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Renal AND Proteinuria [keywords]
- Kidney biopsy results versus clinical parameters on mortality and ESRD progression in 2,687 patients with glomerulonephritis. [JOURNAL ARTICLE]
- Eur J Clin Invest 2014 Apr 21.
Physicians refer proteinuric patients to kidney biopsy in order to clarify the issue of underlying renal disease. We compared kidney biopsy results with classical outcome parameters in a large cohort of patients with biopsy proven glomerulonephritis (GN).In a retrospective analysis, 2,687 patients with different forms of GN from 123 Austrian centres were investigated. Patient characteristics, the diagnosis of GN and its respective subtype and clinical symptoms such as arterial hypertension, hematuria, amount of proteinuria and estimated glomerular filtration rate (eGFR) were tested for their association with all-cause mortality and progression to end stage renal disease (ESRD).During a median follow-up of 129.9 months (IQR 89.6;177.7) 688 patients (25.6%) died and 718 patients required dialysis (29.4%). In multivariate Cox regression analysis age (HR 1.06), female sex (HR 0.71), eGFR (HR 0.74), the diagnosis of GN and its subtypes predicted patient survival (all p<0.01) whereas the amount of proteinuria was not associated with patient survival. The incidence of progression to ESRD was associated with female sex (HR 0.71), eGFR (HR 0.65), amount of proteinuria (HR 1.15) and the diagnosis of GN and its subtypes (all p<0.01). Nephrotic or nephritic syndromes were not associated with patient survival or progression to ESRD and did not add further predictive value to outcome of GN.Our study demonstrates histological diagnosis of GN and its specific subtype predict patient survival and dialysis incidence. Therefore, kidney biopsy should be an integral part of routine diagnostic assessment in patients with any forms of suspected GN. This article is protected by copyright. All rights reserved.
- [Expression of heparanase in kidney of rats with respiratory syncytial virus nephropathy and its relationship with proteinurina]. [English Abstract, Journal Article]
- Sichuan Da Xue Xue Bao Yi Xue Ban 2014 Mar; 45(2):212-5, 224.
To explore the role of heparanase in the pathogenesis of respiratory syncytial virus (RSV) nephropathy in rats model.Twenty 150-200 g Sprague-Dawley (SD) rats (n = 5 per group) were inoculated with 6 x 10(6) PFU RSV and sacrificed on days 4, 8, 14 and 28 postinoculation (RSV4, RSV8, RSV14 and RSV29). Five SD rats inoculated with Dulbecco's minimum essential medium were served as normal control. The expression levels of heparanase protein and mRNA in the rat renal tissue of each group were determined by immunohistochemical staining and real-time quantitative RT-PCR respectively. The proteinurina was also measured and then the relationship between the expression level of heparanase and the 24-hour urinary protein was studied.The rats with RSV nephropathy exhibited higher proteinuria in comparison with normal rats, and the 24-hour urinary protein level was significantly different between each RSV nephropathy group (RSV14 > RSV8 > RSV28 > RSV4, P < 0.05). Compared with normal control, the rats with RSV nephropathy showed up-regulated expression of heparanase protein in glomeruli. The expression levels of heparanase protein in RSV8 and RSV14 group were higher than those in RSV4 and RSV28 group (P < 0.05). There was a linear positive correlation between the expression level of glomerular heparanase protein and the quantity of 24-hour urinary protein (r = 0.783, P < 0.05). Compared with normal control group, the expression levels of heparanase mRNA in the kidney from RSV4, RSV8, RSV14, and RSV28 group were elevated (RSV14 > RSV8 > RSV4 > RSV28 , P < 0.05). There was a linear positive correlation between the expression level of renal heparanase mRNA and the quantity of 24-hour urinary protein (r = 0.725, P < 0.05).The increased expression of heparanase in kidney may be important to the loss of glomerular negative charge in glomerular basement membrane which is involved in the pathogenesis of RSV nephropathy in rats.
- Chronic Kidney Disease Due to Surgical Removal of Nephrons: Relative Rates of Progression and Survival. [JOURNAL ARTICLE]
- J Urol 2014 Apr 16.
Chronic kidney disease(CKD) is associated with a higher likelihood of progression to end stage renal disease and increased mortality rates. However, the etiology of nephron loss may modify the rate of CKD progression and overall survival.Patients with suspected renal malignancy who had a new baseline GFR<60 ml/min/1.73 m(2) six weeks after surgery were divided into two groups: CKD-S (surgically induced CKD, preoperative GFR>60), and CKD-M/S (preexisting CKD due to medical causes followed by surgery). An independent cohort of subjects with CKD-M (entirely due to medical causes) served as a comparator.Renal cancer surgery yielded cohorts with CKD-S (n=1097) and CKD-M/S (n=1053), whereas the CKD-M group consisted of 42,658 subjects. The CKD-M and CKD-M/S groups were older compared to CKD-S patients, had more medical comorbidities, and lower baseline GFR (all p < 0.001). The CKD-M/S group had lower new baseline GFR (37±10) compared to the CKD-S(48±9) and CKD-M(47±10) groups (p<0.001). The probability of progressive decline in renal function (50% decline in GFR or need for dialysis) at 3 years was lowest for CKD-S, intermediate for CKD-M/S and highest for CKD-M, when age, gender, race, comorbidities, and new baseline GFR were taken into account (p<0.001). Non-renal-cancer-related mortality was substantially lower for CKD-S when compared to the other groups(p<0.001).Our data suggest that CKD-S has a lower rate of functional decline and less impact on survival compared to medical causes of CKD. These data have potential implications with respect to classification of CKD and patient counseling for surgical management of various renal disorders, including renal cancer.
- Aliskiren and losartan trial in non-diabetic chronic kidney disease. [JOURNAL ARTICLE]
- J Renin Angiotensin Aldosterone Syst 2014 Apr 17.
This is a report of a clinical trial on the therapeutic efficacy and safety of combined aliskiren and losartan (an angiotensin II receptor blocker (ARB)) versus aliskiren alone and ARB alone in non-diabetic chronic kidney disease (CKD) over a 3-year period.This was a randomised trial in 155 patients with non-diabetic CKD comparing aliskiren (150 mg/day) (n=52) versus losartan (100 mg/day) (n=52) and the third group aliskiren (150 mg/day) combined with losartan (100 mg/day) (n=51). The trial utilised primary renal end points of eGFR <15 ml/min or end-stage renal failure.All three groups had significant reduction of proteinuria (p<0.001 for all). The changes in eGFR, total urinary protein from baseline to each year were not significantly different between the three therapeutic groups.This study in non-diabetic CKD patients showed that combination therapy with aliskiren and ARB was as efficacious as aliskiren alone and ARB alone. There was one patient who developed a non-fatal stroke in the combined aliskiren and ARB group while the other two groups had none.
- Association of a Polymorphism in a Gene Encoding a Urate Transporter with CKD Progression. [JOURNAL ARTICLE]
- Clin J Am Soc Nephrol 2014 Apr 17.
Hyperuricemia predicts a high risk for CKD progression but there is no large clinical trial in humans indicating that this relationship is causal in nature. The rs734553 single-nucleotide polymorphism (SNP) of the GLUT9 urate transporter gene was strongly associated with uric acid (UA) levels in a large meta-analysis.This prospective study adopted the Mendelian randomization approach. The rs734553 SNP was used as an instrumental variable to investigate the relationship between UA and renal outcomes in a cohort of 755 patients with CKD who were enrolled between October 18, 2005, and October 2, 2008. The association between the polymorphism and UA was preliminary confirmed in a series of 211 healthy volunteers enrolled between January 1, 2001, and July 12, 2011, from the same geographic area as the patients with CKD. The study end point was a composite renal-end point (i.e., >30% decrease in the GFR, dialysis, or transplantation). Patients were followed up for a median of 36 months.In healthy individuals, serum UA levels were highest in homozygotes for the T allele (risk allele), intermediate in heterozygotes for the same allele, and lowest in those without the risk allele (P<0.001), but no such relationship was found in patients with CKD. In the CKD cohort, homozygotes (TT) and heterozygotes (GT) for the risk allele had a 2.35 times higher risk (hazard ratio, 2.35; 95% confidence interval, 1.25 to 4.42; P=0.008) of CKD progression. The risk for CKD progression by rs734553 remained unmodified in analyses adjusting for proteinuria, GFR, and other classical and CKD-peculiar risk factors.A GLUT9 polymorphism, which is strongly associated with serum UA levels in healthy individuals of the general population with normal renal function, holds a strong predictive power for CKD progression. These findings are compatible with the hypothesis that the link between UA and CKD progression is causal in nature.
- The effect of combination therapy with rituximab and intravenous immunoglobulin on the progression of chronic antibody mediated rejection in renal transplant recipients. [Journal Article]
- J Immunol Res 2014.:828732.
The treatment for chronic active antibody-mediated rejection (CAMR) remains controversial. We investigated the efficacy of rituximab (RTX) and intravenous immunoglobulin (IVIg) for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m(2)) and IVIg (0.4 g/kg) for 4 days. The efficacy of RTX/IVIg combination therapy (RIT) was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR) before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18), and overall ΔeGFR decreased significantly to 0.4 ± 1.7 mL·min(-1) ·1.73 m(-2) per month 6 months after RIT compared to that observed 6 months before RIT (1.8 ± 1.0, P < 0.05). Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5 ± 2.5 versus 7.0 ± 3.5 protein/creatinine (g/g), P < 0.001). The effect of the RIT on ΔeGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT.
- Renal function preservation with the mTOR inhibitor, Everolimus, after lung transplant. [JOURNAL ARTICLE]
- Clin Transplant 2014 Apr 16.
Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors (CNIs) in solid organ transplantation. Previous data suggest that the use of everolimus as an immunosuppressant drug leads to improvement in renal function. The aim of our study was to establish the effect of everolimus in combination with lower doses of CNIs on renal function among lung transplant recipients. Data regarding renal function and pulmonary function were collected from 41 lung transplanted patients in whom treatment was converted to a combination of everolimus with lower doses of CNIs. Patients transferred to everolimus and low dose CNIs showed an improvement in renal function. Patients who continued treatment with everolimus showed improvement in renal function, as opposed to patients who discontinued the treatment. Subjects without proteinuria at baseline showed a better improvement compared with subjects with proteinuria. The incidence of graft rejection did not increase. We concluded that a protocol that includes everolimus and lower doses of CNIs is effective for preserving renal function in lung transplant recipients with CKD. We also believe that an early implementation of everolimus, before proteinuria occurs or creatinine clearance is reduced, could lead to better outcomes.
- Urinary investigations in the diagnosis and monitoring of monoclonal gammopathies in daily practice. [JOURNAL ARTICLE]
- Ann Biol Clin (Paris) 2014 Apr 1; 72(2):147-152.
The management of monoclonal gammopathies remains a public health issue with an incidence greater than 3% of the population over 50 years. Laboratory investigations, including urinary investigations play a key role in the diagnosis and monitoring of the patients. Urinary investigations are not recommended when screening monoclonal gammopathies. However, the initial laboratory evaluation of the monoclonal gammopathies systematically relies on renal function and proteinuria assessment. Urinary proteins electrophoresis combined with urinary proteins immunofixation are also recommended in the initial evaluation, with the exception of the Waldenström's disease. In some cases, serum investigations remain negative whereas urinary investigations confirm the presence of a monoclonal component. National and international recommendations have also been published about the monitoring of monoclonal gammopathies. The biological monitoring of monoclonal gammopathy of undetermined significance is mostly done by serum tests. Urinary investigations are commonly included in the response criteria in case of multiple myeloma or AL amyloidosis. Laboratory investigations like serum free light chain assay tend to decrease the need of urinary investigations in the monoclonal gammopathies. However, these urinary investigations currently maintain a leading role in the diagnosis and monitoring of monoclonal gammopathies.
- An Update on Coronary Artery Disease and Chronic Kidney Disease. [REVIEW]
- Int J Nephrol 2014.:767424.
Despite the improvements in diagnostic tools and medical applications, cardiovascular diseases (CVD), especially coronary artery disease (CAD), remain the most common cause of morbidity and mortality in patients with chronic kidney disease (CKD). The main factors for the heightened risk in this population, beside advanced age and a high proportion of diabetes and hypertension, are malnutrition, chronic inflammation, accelerated atherosclerosis, endothelial dysfunction, coronary artery calcification, left ventricular structural and functional abnormalities, and bone mineral disorders. Chronic kidney disease is now recognized as an independent risk factor for CAD. In community-based studies, decreased glomerular filtration rate (GFR) and proteinuria were both found to be independently associated with CAD. This paper will discuss classical and recent epidemiologic, pathophysiologic, and clinical aspects of CAD in CKD patients.
- The role of albuminuria in the follow-up of HIV-infected pediatric patients. [JOURNAL ARTICLE]
- Pediatr Nephrol 2014 Apr 16.
In HIV-infected adults, elevated albumin has been associated with increased inflammatory activity, HIV-related nephropathy, and type 2 diabetes. Data on albuminuria in HIV-infected children are very scarce, and guidelines do not include routine determination of urinary albumin/creatinine ratio in this population.We performed a cross-sectional study in a cohort of HIV-infected pediatric patients. Urinary protein/creatinine and albumin/creatinine ratios and hematuria were determined from at least three morning urine samples, and glomerular filtration rate (GFR) was estimated from creatinine levels. Persistent renal damage was defined according to the presence of at least two sequentially abnormal values in one of the parameters. The relationship between renal damage, HIV-related variables, and metabolic comorbidities (dyslipidemia, fat redistribution, glucose intolerance, hypertension) was investigated.Symptom-free renal damage was observed in 13 of 68 patients (19.1 %) and mainly consisted of persistent proteinuria (17.6 %); glomerular proteinuria was twice as prevalent as tubular proteinuria. GFR were normal in all cases. No relationship between renal markers and HIV-related variables or metabolic comorbidities was observed.Mild proteinuria affected approximately one fifth of patients in our cohort. The determination of albuminuria allowed the differentiation between glomerular and tubular proteinuria, although no relationship with metabolic comorbidities was observed.