Clinical Proteinuria Research Articles

The impact of insulin pump therapy to oxidative stress in patients with diabetic nephropathy

BackgroundThe oxidative stress resulting from increased production of ROS plays a crucial role in the development of diabetic complications. We aim to explore the relationships between oxidative stress, diabetic nephropathy (DN) and short-term insulin pump intensive therapy (insulin therapy).MethodsLevels of 8-hydroxy-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), glutathione (GSH), superoxide dismutase (SOD) and Interleukin-6 (IL-6) were estimated before and after 2 weeks of insulin therapy in normal group (NC) and type 2 diabetic (DM) with normal albuminuria (NA), microalbuminuria (MA) and clinical albuminuria (CA).ResultsIn DM group, levels of 8-OHdG and 3-NT were higher than those in NC group (P < 0.05); GSH and SOD were lower (P < 0.05). And their levels changed with urine albumin–creatinine ratio (P < 0.05). After insulin therapy, these derangements were significantly ameliorated and the changes in NA and MA groups were more significant than CA group (P < 0.05). Correlation analysis showed glycated hemoglobin, the course of disease, the HOME-IR and fasting plasma glucose were positively correlated with 8-OHdG and 3-NT, but negatively correlated with GSH and SOD.ConclusionsThe oxidative stress gradually increased with the magnitude of DN, and insulin pump intensive therapy can significantly ameliorate the derangements in the early stage of DN.Trial registration NCT03174821

Proteinuria and the Clinical Course of Dobrava-Belgrade Hantavirus Infection

Purpose: Human infection with Dobrava-Belgrade virus (DOBV) in Northern Germany causes a mild form of hantavirus disease predominantly characterized by acute kidney injury due to interstitial nephritis. We evaluated the largest number of DOBV-infected patients so far regarding clinical course, proteinuria, and prognostic markers. Patients and Methods: Patients with DOBV-associated hantavirus disease admitted to the Renal Division of the University of Lübeck (Germany) between 1997 and 2012 were included in this study. Symptoms, clinical course, laboratory parameters, and urinary protein analysis were investigated at admission (baseline, t₀), 3–5 days (t_3–5), 10–17 days (t_10–17), and after 1 year of follow-up (t₃₆₅). Results: Of the 34 patients (male/female ratio: 23/11; age: 41 ± 14 years) included in the study, 4 underwent hemodialysis (HD). Glomerular filtration rate was 17 ± 14 mL/min at t₀ and increased to 27 ± 26 mL/min (t_3–5), 57 ± 20 mL/min (t_10–17), and 84 ± 16 mL/min (t₃₆₅). Albuminuria and tubular proteinuria (α₁- and β₂-microglobulin) decreased during follow-up; the urinary α₁-microglobulin concentration in patients who required HD was significantly higher than that in patients not requiring HD (t₀: 186 ± 51 vs. 45 ± 26 mg/g creatinine; t_3–5: 87 ± 14 vs. 32 ± 16 mg/g creatinine; t_10–17: 63 ± 18 vs. 28 ± 12 mg/g creatinine; p < 0.001). Conclusions: DOBV infection of inpatients in Northern Germany is associated with severe kidney injury that recovers within a few weeks and normalizes within 1 year. Tubular proteinuria is associated with the severity of kidney injury and the necessity of renal replacement therapy in these DOBV-infected patients.

The relationship between urine neutrophil gelatinase-associated lipocalin and microinflammation in patients with hypertensive nephropathy

Objective To investigate the variation of urine neutrophil gelatinase-associated lipocalin (NGAL) level in hypertensive with early renal injury, and its relationship with micro-inflammation. Methods One hundred and seven patients with primary hypertension were recruited in this study. According to the level of urinary albumin excreting rate(UAER), these 107 patients were divided into three subgroups: 30 patients in normal albumin (NA) level in urine, 39 patients in micro albumin(MA)level in urine and 38 patients in clinical albuminuria(CA) . Another 40 healthy adults were recruited in this study as control group. Each patient’s testing results of NGAL and hypersensitive C-reactive protein(hsCRP) were recorded. The level of serum Cr was also recorded, the value of estimated glomerular filtration rate (eGFR) was calculated according to the formula of Cockroff-Gault. Results The level of urine NGAL in patients with hypertension was obviously higher than in control group with healthy adults (P<0.01). Furthermore, the difference of NGAL could be seen inside the group of hypertension: the level of urine NGAL in subgroup of MA and subgroup of CA was significant higher than in subgroup of NA (P<0.01). Additionally, the level of urine NGAL was negative correlation to eGFR (r=-0.403, P<0.01), and positive to serum hsCRP (r=0.451, P<0.01). Conclusions The level of urine NGAL increases obviously in patients with hypertensive nephropathy, and a positive correlation exists between the severity degree of renal injury and inflammation factor. It imply that the level of NGAL can be served as a tool for diagnosis of early renal injury and micro-inflammation in patients with hypertensive nephropathy. Key words: Hypertension; Kidney Diseases; Lipocalins; Inflammation

Dual Kidney Transplantation: A Review of Past and Prospect for Future.

Kidney transplantation (KT) is one of the treatment options for patients with chronic kidney disease. The number of patients waiting for kidney transplantation is growing day by day. Various strategies have been put in place to expand the donor pool. Extended criteria donors are now accepted more frequently. Increasing number of elderly donors with age > 60 years, history of diabetes or hypertension, and clinical proteinuria are accepted as donor. Dual kidney transplantation (DKT) is also more frequently done and experience with this technique is slowly building up. DKT not only helps to reduce the number of patients on waiting list but also limits unnecessary discard of viable organs. Surgical complications of DKT are comparable to single kidney transplantation (SKT). Patient and graft survivals are also promising. This review article provides a summary of evidence available in the literature.

Proteinuria in preeclampsia: Not essential to diagnosis but related to disease severity and fetal outcomes.

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality globally and proteinuria can be one of the cardinal features of this disease. However, studies about the association of the amount of proteinuria and the severity of preeclampsia, and perinatal outcomes are limited. Data on 239 women with preeclampsia were retrospectively collected from a university teaching hospital from September 2011 to June 2013 and analysed. Data included all clinical parameters and proteinuria in a 24h urine collection. In cases of severe preeclampsia, significantly fewer patients had proteinuria levels <0.3g/L in comparison to any of the other groups with proteinuria >0.3g/L, but there was no difference in cases of severe preeclampsia when proteinuria levels were >0.3g/L. Furthermore, when proteinuria levels were >0.3g/L, the frequency of severe preeclampsia in each group was significantly higher than the frequency of mild pre-eclampsia cases. Time of onset was significantly earlier in patients with proteinuria >3g/L in a 24h urine collection, but time between the onset of preeclampsia and delivery was not correlated with the amount of proteinuria. The birth weight was significantly lower in patients with proteinuria >3g/L. The incidence of fetal growth restriction or stillbirth was significantly higher in patients with proteinuria >5g/L. Our data demonstrate that the amount of proteinuria is not associated with the severe of preeclampsia, once proteinuria is detected, but is related to the severity of preeclampsia. The adverse fetal outcomes appear to be the function of prematurity rather than proteinuria itself.

Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies.

Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37). Cortical IF, TA and II were quantified (%) on digitized whole-slide biopsy images, by five pathologists with high inter-reader agreement (intra-class correlation coefficient >0.8). Tubulointerstitial messenger RNA expression was measured in a subset of patients. Multivariable Cox proportional hazards models were fit to assess association of IF with the composite of 40% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD) and separately as well, and with complete remission (CR) of proteinuria. IF was highly correlated with TA (P < 0.001) and II (P < 0.001). Median IF varied by diagnosis: FSGS 17, IgAN 21, MN 7, MCD 1 (P < 0.001). IF was strongly correlated with baseline eGFR (P < 0.001) and proteinuria (P = 0.002). After adjusting for clinical pathologic diagnosis, age, race, global glomerulosclerosis, baseline proteinuria, eGFR and medications, each 10% increase in IF was associated with a hazard ratio of 1.29 (P < 0.03) for ESRD/40% eGFR decline, but was not significantly associated with CR. A total of 981 genes were significantly correlated with IF (|r| > 0.4, false discovery rate (FDR) < 0.01), including upstream regulators such as tumor necrosis factor, interferon gamma (IFN-gamma), and transforming growth factor beta 1 (TGF-B1), and signaling pathways for antigen presentation and hepatic fibrosis. The degree of IF is associated with risk of eGFR decline across different types of proteinuric glomerulopathy, correlates with inflammatory and fibrotic gene expression, and may have predictive value in assessing risk of progression.

Abstract 179: Determinants of Cerebral Microbleeds in Acute Ischemic Stroke Patients With Non-valvular Atrial Fibrillation: SAMURAI-NVAF Study

Background and Purpose: Cerebral microbleeds (CMBs) are now considered to be one of the neuroimaging markers of cerebral small vessel disease. It has been reported that CMBs are associated with age, hypertension, cognitive impairment, and use of antithrombotic drugs. We aimed at identifying factors associated with the presence of CMBs among acute ischemic stroke patients with non-valvular atrial fibrillation (NVAF) who participated in the multicenter Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-NVAF study. Methods: Acute ischemic stroke/transient ischemic attack (within 7 days of onset) patients with NVAF who underwent T2*-weighted images on magnetic resonance imagings at baseline were included in the analysis. Factors associated with the presence of CMBs were assessed in univariable and multivariable logistic regression models. Results: Of 1,099 (77.6±10.0 years, 620 male) participants, 256 (23.2%) had CMBs: single CMB in 96 (8.7%), 2-4 of CMBs in 109 (9.9%), and ≥5 CMBs in 51 (4.6%). The presence of CMBs was associated with age [per 10 years, odds ratio (OR) 1.21; 95% confidence interval (CI) 1.02-1.44], past history of stroke (OR 1.52; 95% CI 1.09-2.11), and advanced cognitive impairment (OR 1.64; 95% CI 1.02-2.61) in multivariable analysis adjusted for sex, hypertension, arterial disease, ever smoking, premorbid antithrombotic medications, and estimated glomerular filtration rate. Among 514 patients (46.8% of the participants) with the data of urinary albumin, clinical albuminuria (urinary albumin ≥300 mg/gCr) and past history of stroke were identified as independent factors associated with CMBs (OR 1.91; 95% CI 1.06-3.42 and 1.67; 1.04-2.66, respectively). Conclusions: Approximately one fourth of acute ischemic stroke patients with NVAF had CMBs. Past history of stroke and clinical albuminuria were identified as independent determinants of CMBs on top of established ones. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01581502.

Cystatin C in the early diagnosis of diabetic nephropathy and its correlation with albuminuria

Background: Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycaemia. The metabolic dysregulations associated with DM causes secondary pathophysiological changes in multiple organ systems which result in various complications, responsible for the morbidity and mortality associated with the disease.Methods: The present study was undertaken in the Department of Medicine in collaboration with the Department of Biochemistry, of SGRDIMSR, Vallah, Sri Amritsar, Punjab, India. The present hospital based study was undertaken with a total number of 100 patients.Results: The mean Cystatin C values in Group A were 1.73 and mean Cystatin C values in group B were 2.07. The results show that the Cystatin C values were raised even in the patients in whom clinical albuminuria had not yet started.Conclusions: serum Cystatin C may be considered as an early marker, than microalbuminuria and serum creatinine, the commonly used marker for nephropathy, for declining renal function, in diabetic subjects. Further studies in larger population are needed to confirm this result.

Exercise-induced albuminuria and circadian blood pressure abnormalities in type 2 diabetes.

AIMTo investigate the relationship between circadian variations in blood pressure (BP) and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes (T2D) patients.METHODSWe conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical proteinuria and normal creatinine clearance. In each participant, we recorded the BP using ambulatory blood pressure monitoring (ABPM) for 24-h, and albuminuria at rest and after a standardized treadmill exercise.RESULTSWe enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure (SBP) of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg (P = 0.004), and mean diurnal diastolic blood pressure (DBP) of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg (P = 0.002). There was a significant difference between albuminuria at rest [median = 23 mg, interquartile range (IQR) = 10-51] and after exercise (median = 35 mg, IQR = 23-80, P < 0.001). Patients with exercise induced albuminuria had an increase in nocturnal BP values on all three components (128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure), as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP (83 vs 86, P = 0.03) than resting albuminuria.CONCLUSIONExercise induced albuminuria is associated with an increase in nocturnal BP values in T2D patients.

Expression levels of serum vasohibin-1 in type 2 diabetes mellitus patients with different excretion rates of urinary albumin and its clinical significance

Objective To investigate the expression levels of serum vasohibin-1(VASH-1)in type 2 diabetes mellitus(T2DM)patients at different stages of urinary albumin to creatinineratio(UACR)and to attempt to investigate the relationship between VASH-1 and inflammation and fibrosis in the pathogenesis of diabetic nephropathy(DN), one of the microvascular complications of T2DM. Methods 486 patients with T2DMwere divided into four groups: normal albuminuria [UACR 300 mg/g, n=106], and clinical albuminuria hypertensive [UACR>300 mg/g, with hypertension, n=124] groups. Age, course, serum levels ofVASH1, inflammation markers(CRP, ESR)and fibrosis marker(TGF-β1)with other biochemical indicators were measured, and 130 normal control subjects were also included. Results Compared with normal control group, the levels of UACR, HbA1C, ESR, CRP, TGF-β1 and VASH-1 in groups ofnormal albuminuria, microalbuminuria, clinical albuminuria, and clinical albuminuria hypertensive were significantly higher(P<0.05). Pearson correlation analysis showed that levels of VASH-1 were positively correlated with UACR, HbA1C, ESR, CRPand TGF-β1(r=0.521, 0.261, 0.519, 0.523, 0.479, P<0.001), while multivariate regression analysis showed that levels of UACR, HbA1C, ESR, CRP and TGF-β1 were important factors affecting serum VASH-1 levels. Conclusion Serum levels of VASH-1 may become new biomarkers of early diagnosis of DN. Consequently, VASH-1 level may provide a new pattern and direction of inflammation and fibrosis for consideration in diabetic kidney damage. (Chin J Endocrinol Metab, 2016, 32: 647-651) Key words: Diabetic nephrophathy; Transforming growth factor--β1; Vasohibin-1

IgA nephropathy clinicopathologic study following the Oxford classification: Progression peculiarities and gender-related differences

Background and aimImmunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease worldwide and one of the main causes of chronic kidney disease. We aimed to investigate clinicopathological correlations in IgAN patients by gender. Materials and methodsThe study was based on a retrospective analysis of renal biopsy data and clinical manifestations of the disease. Consecutive 73 biopsy-proven IgAN cases of male (62%) and female (38%) patients were investigated. Renal biopsies were reviewed using the new Oxford classification assessing the MEST (mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis/adhesion, tubular atrophy/interstitial fibrosis) score. The most powerful IgAN prognostic risk factors, morphological (segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis) as well as clinical (proteinuria and hypertension) were taken into account in the correlation analysis. The mean rate of renal function decline was expressed as a slope of eGFR during the follow-up (FU) dividing delta GFR with the FU years. ResultsThe mean age of the patients was 33.7 years (range, 16–76). Follow-up data were available for 64 patients with the mean follow-up of 4.1 years. The mean proteinuria at biopsy was 0.79g/24h. The mean arterial pressure (MAP) was 94.5±16.7mmHg and 7% of the patients were hypertensive. The initial mean estimated glomerular filtration rate (eGFR) was 94.9±30.7mL/min, at the end of the follow-up it was 86.2±27.1mL/min. The mean rate of renal function decline was −3.4±11.9mL/min/1.73m2 per year in males (P<0.05) and −0.7±5.3mL/min/1.73m2 per year in females. The Spearman correlation analysis confirmed a higher MEST score in the whole cohort and in males correlated with disease progression. In patients with proteinuria below 1.0g/24h, disease progression was faster in males. ConclusionsAccording to the correlation analysis of the main prognostic risk factors, affecting the progression of IgAN, we can conclude that IgA nephropathy in males progresses more rapidly compared to females.

Prevalence and determinants of microalbuminurea among type 2 diabetes mellitus patients, Baghdad, Iraq, 2013

Microalbuminuria (MAU) is an early marker of diabetic nephropathy (DN), which accounts for a significant reduction in life expectancy of diabetic patients. The progression of DN from the appearance of clinical proteinuria to end stage renal failure is usually irreversible. Increased levels of urinary albumin secretion may represent a more generalized vascular damage. This is the first study conducted in Iraq to determine the prevalence and potential risk factors of MAU among Type 2 diabetes mellitus (T2DM) patients. A cross-sectional study was conducted on a systematic random sample of 224 eligible T2DM patients aged 25-64 years attending a DM clinic in Baghdad. A questionnaire was developed to gather basic and clinical data, besides anthropometric measurements, and laboratory assessment of lipid profile, HbA1c, serum creatinine, albumin, and microalbumin/creatinin in urine. MAU was defined as albumin/creatinine ratio 30-300 mg/g on two occasions. Only 36 cases (16.1%) had MAU. A statistical significant association found between MAU and educational level (P = 0.009), family history of hypertension (P = 0.024) and DN (P = 0.013), history of hypertension (P = 0.001), duration of angiotensin-converting-enzyme inhibitor drug intake in hypertensive patients (P = 0.001), body mass index (BMI) (P = 0.014), and waist to hip ratio (P = 0.006). Logistic regression analyses revealed two independent risk factors influencing MAU: diastolic blood pressure [odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.007-1.118] and BMI (OR = 1.17, 95% CI: 1.037-1.220). The prevalence of MAU is not low among DM patients. Mandatory screening of all DM patients and amelioration of the assigned significant risk factors are recommended.

The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy.

ObjectiveTristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes.MethodsEighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR).ResultsSerum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05).ConclusionThese results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.

Death, end-stage renal disease and renal function decline in patients with diabetic nephropathy in French cohorts of type 1 and type 2 diabetes.

Microvascular complications are a common feature of diabetes but additional research is needed regarding diabetic nephropathy endpoints in type 1 and type 2 diabetes. We compared 277 type 1 diabetes patients with 942 type 2 diabetes patients, with clinical proteinuria and no endstage renal disease (ESRD) at baseline, prospectively followed for death, ESRD and decline in estimated glomerular filtration rate (eGFR, all available measures). The incidence rate of death was 67.0 (95% CI 59.2, 74.8) vs. 24.6 (95% CI, 19.0, 30.2) per 1,000 patient-years, in type 2 diabetes and type 1 diabetes, respectively. Unadjusted risk for death was greater for type 2 diabetes patients (HR 3.423; 95% CI, 2.501, 4.683; p<0.0001), but the difference did not persist after adjustment for age (HRage-adj 0.859; 95% CI 0.581, 1.269; p=0.445). The incidence rate of ESRD was 18.4 (95% CI 14.2, 22.5) vs. 47.1 (95%CI 38.4, 55.9) per 1,000 patient-years, in type 2 diabetes and type 1 diabetes, respectively. Unadjusted risk for ESRD was lower in type 2 diabetes (HR 0.399; 95% CI 0.287, 0.554; p<0.0001), but the difference did not persist after adjustment for sex, age and baseline serum creatinine (HRadj 0.989; 95% CI 0.597, 1.639; p=0.965). In a mixed linear model, eGFR decline was not significantly different in type 2 vs. type 1 diabetes (difference in slope −0.19 [0.28] ml min(−1) 1.73 m(−2) year(−1); p=0.512). In diabetic nephropathy, once baseline risk factors were taken into account the risk for death, ESRD and renal function decline did not significantly differ between type 1 diabetes and type 2 diabetes.

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Objective: Microalbuminuria (MA) is known to predict the onset of clinical proteinuria and chronic renal failure in diabetes mellitus. More recently, MA has been found to be an independent risk factor for cardiovascular disease in non diabetic populations. The present study was designed to investigate the prevalence of microalbuminuria and factors that associate with urine excretion of albumin in the population of Blida. Design and method: 2920 Participants in our specialized consultation were enrolled in this study. Besides the routine checkup program (an interview regarding health status, physical examination, chest X-ray, electrocardiography, and laboratory assessment of cardiovascular risk factors). For MA, spot urine samples were collected in the early morning and microalbuminuria was defined as, a urinary albumin excretion between 30 and 300 mg/l. These patients also underwent determination of ambulatory blood pressure monitoring. All calculations and statistical analyzes are processed by the SPSS 17.0. Results: The prevalence of MA in hypertensive population was 32%.The blood pressure of participants was 138 ± 16/78 ± 13 mmHg and 39.8% and 14.1% of participants were with hypertension and diabetes mellitus, respectively. Urine albumin was detected in 40.1% of cases. Mean age of 59.71 ± 13.56 years. Body mass index was > 30 kg/m2 in 58.2% of cases. Prevalence of Hyperglycemia was 23% with MA> 30 mg/l. Multivariate regression analysis revealed that abnormal albuminuria was correlated with systolic blood pressure, estimated 24 hours urinary salt excretion, and fasting plasma glucose after adjustment for possible factors (p < 0.0001). Conclusions: The prevalence of microalbuminuria increases with increase in age, body mass index and duration of hypertension. From this study, it is conceived that MA can be used as a predictor of future cardiovascular events in hypertensive patients.

The cellular signature of urinary immune cells in Lupus nephritis: new insights into potential biomarkers

IntroductionUrinary T cells represent a reliable noninvasive biomarker for proliferative Lupus nephritis (LN). Little is known about the presence of T cell subsets, B cells and macrophages in the urine although they may further improve the validity of urinary cellular biomarkers for LN.MethodsWe analyzed contemporaneous blood and urine samples of patients with active LN (n = 19), other Systemic Lupus Erythematosus (SLE) patients (n = 79) and urine samples of patients with diabetic nephropathy (DN; n = 14) and anti-neutrophil cytoplasmatic antibody (ANCA) associated vasculitis (AAV; n = 11) by flow cytometry.ResultsNumbers of urinary T cells, B cells and macrophages correlated with disease activity and were significantly higher in the active LN group. Urinary T cells showed excellent distinction of patients with active LN, CD8+ T cells (AUC of ROC = 1.000) and CD4+ T cells (AUC = 0.9969) alike. CD19+ B cells (AUC = 0.7823) and CD14+ macrophages (AUC = 0.9066), as well as the clinical standard proteinuria (AUC = 0.9201), failed to reach these high standards. Patients with DN or AAV also showed increased urinary cell counts, although the CD4/CD8-ratio was significantly lower in SLE compared to in DN (p = 0.0006). Urinary CD4+ T cells of active LN patients proved to be mainly of effector memory phenotype and expressed significantly more CD40L and ki67 than corresponding blood cells. Urinary Treg counts correlated with disease activity.ConclusionsDespite of detectable urinary cell counts for B cells and macrophages, T cells remain the best urinary cellular biomarker for LN. A low CD4/CD8-ratio seems to be characteristic for LN.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0600-y) contains supplementary material, which is available to authorized users.

Autonomic dysfunction independently predicts poor cardiovascular outcomes in asymptomatic individuals with type 2 diabetes in the DIAD study.

Objective:The primary aim of this secondary analysis was to determine whether cardiac autonomic neuropathy independently predicted adverse cardiac outcomes in asymptomatic individuals with type 2 diabetes. Additional aims include the determination of the correlation of standard autonomic testing measures and power spectral analysis of heart rate variability, and the association of diabetes-related and cardiac risk factors with cardiac autonomic neuropathy measures.Methods:Cardiac autonomic neuropathy was assessed at the study entry into the Detection of Ischemia in Asymptomatic Diabetics study, using autonomic heart rate and blood pressure testing, and power spectral analysis of heart rate variability. All participants were prospectively followed for the composite clinical outcome of cardiac death, acute coronary syndromes, heart failure, or coronary revascularization.Results:Over 5 years of follow-up, 94 of 1119 (8.4%) subjects developed symptomatic cardiac disease. In unadjusted bivariate analyses, abnormalities in several cardiac autonomic neuropathy tests, including lower Valsalva and Standing Heart Rate Ratios, higher resting Heart Rate, greater systolic blood pressure decrease on standing, and lower low-frequency power, were predictive of symptomatic disease. Independent predictors of poor cardiac outcome were a lower Valsalva Heart Rate Ratio, non-Black ethnicity, longer diabetes duration, higher glycated hemoglobin (HbA1c), insulin use, reported numbness in the extremities, higher pulse pressure, family history of coronary artery disease, and higher waist-to-hip ratio. Clinical factors independently associated with a lower Valsalva Heart Rate Ratio were insulin use, clinical proteinuria, higher pulse pressure, use of angiotensin-converting enzyme inhibitor and non-Black ethnicity.Conclusion:Cardiac autonomic neuropathy predicted adverse cardiac outcomes in asymptomatic type 2 diabetes without known cardiac disease. Clinical variables may help to identify patients who might have cardiac autonomic neuropathy and warrant consideration for autonomic testing.

Glycemic control according to glomerular filtration rate in patients with type 2 diabetes and overt nephropathy: A prospective observational study

Background and ObjectiveType 2 diabetes (T2D) and chronic kidney disease (CKD) are closely linked. This study aimed to describe and analyze the relations between renal function and glycemic control in T2D patients with overt nephropathy. Patients and methodsData were collected from a French observational prospective multicenter study. Patients included were adults with T2D, clinical proteinuria and an estimated glomerular filtration rate (eGFR) over 15mL/min/1.73m2. Baseline data and glycemic control after a one-year follow-up are presented here. ResultsData from 986 adult patients were analyzed. Mean age was 70 years. Mean eGFR was 42mL/min/1.73m2, 66% of patients had proteinuria above 1g/day. HbA1c was higher in patients with lower eGFR in a model adjusted to age, gender, body mass index, hemoglobin level and erythropoietin use. Statistical significance was lost when stepwise multivariate analysis took into account the type of pharmacological treatment used to treat hyperglycemia.The type of antidiabetic agents differed across eGFR strata. Below 60mL/min/1.73m2, the use of metformin declined while the use of insulin increased.After one year of follow up, 35% of patients had persistently poor or worsened glycemic control (HbA1c>8%). The only covariate independently associated with this characteristic was the duration of insulin therapy. ConclusionIn patients with T2D and overt nephropathy, the observed correlation of low eGFR with high HbA1c was not predicted by eGFR. Our data rather underscore a different use of antidiabetic treatments in patients with advanced renal dysfunction, and the difficulty to improve glycemic control in patients with long standing insulin therapy.

Race and other risk factors for incident proteinuria in a national cohort of HIV-infected veterans.

Proteinuria in human immunodeficiency virus (HIV)-infected individuals has been associated with poorer outcomes. We examined risk factors associated with the development of proteinuria in a national registry of HIV-infected veterans. A total of 21,129 HIV-infected veterans of black and white race without preexisting kidney disease were receiving health care in the Veterans' Health Administration (VHA) medical system between 1997 and 2011. Using the VHA electronic record system, we identified kidney-related risk factors (hypertension, diabetes, and cardiovascular disease) and HIV-related risk factors (CD4 lymphocyte count, HIV RNA level, hepatitis C virus, and hepatitis B virus) for developing proteinuria. Proteinuria was defined by 2 consecutive dipstick measures of 1 or higher. The Fine-Gray competing risk model was used to estimate association between clinical variables and incident proteinuria, while accounting for intervening mortality events. During follow-up (median = 5.3 years), 7031 patients developed proteinuria. Overall, black race compared with white race was associated with a higher risk of proteinuria {hazard ratio [95% confidence interval (CI)] = 1.51 [1.43 to 1.59]}, but the association was stronger at younger ages (P interaction <0.001). Age-stratified risk of proteinuria for blacks relative to whites was greatest among veterans <30 years [2.19 (1.66 to 2.89)] and the risk diminished with increasing age [1.14 (0.97 to 1.34) for >60 years]. We found the race difference to be stronger for the outcome of 2 or higher proteinuria [2.13 (1.89 to 2.39)]. Both HIV-related and traditional risk factors were also associated with incident proteinuria (P < 0.05). Compared with whites, risk of proteinuria was higher in black veterans with HIV infection, particularly at younger ages. In both races, HIV- and kidney-related risk factors were associated with higher proteinuria risk.

Study on effects of keto acid tablets combined with captopril therapy proteinuria in diabetic nephropathy patients

Objective To investigate the clinical effect of keto acid tablets combined with captopril therapy proteinuria in diabetic nephropathy patients.Methods In our hospital from 2011 December to 2013 December among patients diagnosed as diabetic nephropathy and clinical proteinuria were sampled,we selected 100 cases of patients and randomly divided them into two groups,and then observed and compared,control group was given insulin intensive glucose control,oral captopril,the experimental group on the basis of strengthening blood sugar control,was given keto analogues tablets for treatment,plasma albumin level and clinical therapeutic efficacy were compared in two groups with proteinuria excretion.Results The total effective rate of the experimental group (98％) was significantly better than that of the control group (82％),the difference was statistically significant (P＜ 0.05).The experimental group with 16 cases of 24 h proteinuria ＜ 0.5g/L,3 cases of 0.5-1.0 g/L; the control group had 15 cases 24 h proteinuria ＜ 0.5 g/L,4 cases of 0.5-1.0 g/L; 1 case in experimental group plasma albumin content ＜ 25 g/L,2 cases in the control group,there was statistical significant difference between two groups (P ＜ 0.05).Conclusion The clinical proteinuria in diabetic nephropathy patients,based on the low protein diet and blood lipids,blood glucose,blood pressure control and treatment,with keto analogues tablets combined treatment for captopril,can help to reduce proteinuria,and control the progress of diabetic nephropathy. Key words: Acid tablets; Captopril; Diabetic nephropathy; Proteinuria