Proteinuria has been recognized as a common feature in many forms of chronic kidney disease (CKD). As traditional medications for proteinuric nephropathy, such as blockade of the renin-angiotensin system (RAS), has only achieved limited clinical success, more effective renoprotective strategies need to be explored. Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) have recently shown promise as a therapeutic tool in acute kidney injury (AKI) models. The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in proteinuric nephropathy models is unknown. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, I first examined the potential effect of BM-MSCs in albumin-induced pro-inflammatory response and epithelial-to-mesenchymal transition (EMT) in PTECs. The unstimulated BM-MSCs exerted moderate suppressive effect on tubular inflammation as only albumin-induced CCL-2 and CCL-5 expression was attenuated in PTECs. When concomitantly stimulated by albumin excess, however, BM-MSCs remarkably suppressed albumin-induced tubular IL-6, IL-8, TNF-α, CCL-2, and CCL-5 expression, suggesting albumin overloaded milieu to be a prerequisite for them to fully exhibit their anti-inflammatory effects. This effect was mediated via deactivation of tubular NF-κB signaling as BM-MSCs prevented the overexpression of p-IκB and nuclear translocation of NF-κB. In addition, albumin-induced tubular EMT, as shown by the loss of E-cadherin and induction of α-SMA, FN-1 and collagen IV in PTECs, was also prevented by BM-MSC co-culture. To dissect the mechanism of action, I next explored the paracrine factors secreted by BM-MSCs under an albumin-overloaded condition and studied their contribution to the protective effect on tubular inflammation and EMT. Albumin-overloaded BM-MSCs per se overexpressed 34 paracrine factors, of which hepatocyte growth factor (HGF) and TNFα-stimulating gene (TSG)-6 were regulated by P38 and NF-κB signaling. These paracrine factors suppressed both the proinflammatory and profibrotic phenotypes in albumin-induced PTECs. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. Finally, in albumin-overloaded mice, a well established murine model reminiscent of human CKD, treatment with mouse BM-MSCs markedly reduced BUN, tubular CCL-2 and CCL-5 expression, interstitial macrophage, α-SMA and collagen IV accumulation independent of changes in proteinuria, together with upregulated renal cortical expression of HGF. Exogenous BM-MSCs were detected in their kidneys by PKH-26 staining. Collectively, these in vitro and in vivo data suggest a modulatory effect of BM-MSCs on albumin-induced tubular inflammation and fibrosis and underscore a therapeutic potential of BM-MSCs for CKD in the future. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Background: The most commonly employed screening method for proteinuria is a semi- quantitative dipstick urinalysis, but it has been shown to be inaccurate in pregnancy. New developments in the assessment of proteinuria have included the use of urinary albumin measurements. The Clinitek Microalbumin Reagent Strip (Bayer Healthcare LLC, USA) is a semi-quantitative dipstick test. It is used to measure the spot urinary microalbumin to creatinine ratio that is read using the Clinitek 50 portable urine chemistry analyzer. Aims We embarked on a pilot study to validate the Clinitek 50 system by determining the accuracy of spot urinary microalbumin to creatinine ratio dipsticks and conventional visual dipsticks (Makromed) compared to the laboratory urinary microalbumin to creatinine ratio quantification to detect significant proteinuria in normotensive and hypertensive antenatal attendees. The accuracy of spot urinary microalbumin to creatinine ratio dipsticks and conventional visual dipsticks were then compared to a 24 hour urinary protein (gold standard) to detect significant proteinuria in hypertensive disorders of pregnancy. We then determined the role of proteinuria as assessed by the diagnostic accuracy of both the 24 hour urinary protein (gold standard) and the spot urinary microalbumin to creatinine ratio dipstick, in pregnancy outcomes of these participants. Methods This was a prospective study conducted at hospitals serving the Durban Metropolitan region in South Africa. To validate the urinary microalbumin to creatinine ratio dipstick, fifteen normotensive healthy pregnant women and 11 women with new onset hypertension in pregnancy were recruited .Each women had a spot midstream urine, which was assessed for proteinuria using a semi-quantitative visual dipstick (Makromed) and analysed using the semi-quantitative urinary microalbumin to creatinine ratio dipsticks (Clinitek® Microalbumin) read on the Clinitek® 50 urine chemistry analyser. A result of 1 + on visual dipsticks and a spot urinary microalbumin to creatinine ratio UAC of > 300mg/g (33.9mg/mmol) was considered as positive for significant proteinuria. The results were compared to the laboratory quantitative measurement of the urinary microalbumin to creatinine ratio. The study group comprised 163 women presenting with newly diagnosed hypertension during pregnancy after 20 weeks of gestation, being recruited from antenatal clinics. Each participant had a spot urine sample that was tested by trained midwives for proteinuria using a semi-quantitative visual dipstick (Makromed). Participants were admitted to the ward where a spot midstream urine sample was collected and analysed using the semi-quantitative urinary microalbumin to creatinine ratio dipsticks. A 24 hour quantitative urinary protein analysis was completed. The results of the urinary microalbumin to creatinine ratio dipsticks and conventional visual dipsticks were compared to the 24 hour urinary protein (gold standard) to detect significant proteinuria. A urinary microalbumin to creatinine ratio of < 300mg/g (nil and trace on visual urine dipsticks) was considered to be a negative result. A urinary microalbumin to creatinine ratio 300 mg/g (1+ to 4+ on visual urine dipsticks) was considered to be a positive result. Urinary protein 0.3 g/24 hours was considered significant proteinuria. The outcomes of pregnancy in 2 sub-categories viz. those with and without significant proteinuria were compared using the 24 hr urinary protein measurement. A secondary analysis of outcomes of pregnancy was performed by subcategorizing the participants according to the diagnostic accuracy of the urinary microalbumin to creatinine ratio dipsticks. In the 26 patients enrolled in the initial study , the visual dipstick had a sensitivity of 25% ( 95% CI [0.04-0.64] ) and specificity of 89% ( 95% CI [0.64 -0.98]).The urinary microalbumin to creatinine ratio dipsticks had a sensitivity of 88% ( 95% CI [0.47-0.99]), specificity of 89% (95% CI [0.64-0.98]), negative predictive value (NPV) of 94% (95% CI [0.69-1.00]) and positive predictive value (PPV) of 78% (95% CI [0.40-0.96]). In the 163 patients subsequently enrolled the visual dipstick had a sensitivity of 51 % ( 95% CI [0.41-0.61]) and specificity of 91% (95% CI [0.81-0.96]) .The PPV and NPV was 89 %( 95% CI [0.77-0.95]) and 58% (95% CI [0.48-0.67]) respectively. The urinary microalbumin to creatinine ratio dipsticks had a sensitivity of 63% (95% CI [0.52-0.72]) and specificity of 81 % (95% CI [0.70-0.89]). The PPV was 82% (95% CI [0.71-0.90]) and NPV was 62% (95% CI [0.51-0.71]). Our results show that in hypertensive pregnant women, significant proteinuria determined by the quantitative 24 hour urinary protein is associated with delivery at an earlier gestational age, increased induction of labour and lower birthweights compared to the non-proteinuric hypertensives (gestational hypertension). There is also a trend towards an increased maternal morbidity and perinatal mortality. When the groups were classified into pre-eclampsia and gestational hypertension using the diagnostic accuracy of the urinary microalbumin to creatinine ratio dipsticks, there were no differences in the clinical outcomes between the false negatives and true negatives except a trend towards a higher caesarean section rate in the false negatives. Conclusion The urinary microalbumin to creatinine ratio dipstick read on the Clinitek 50 system provides a semi – quantitative result of the urinary microalbumin to creatinine ratio that has good sensitivity and specificity. Furthermore, the urinary microalbumin to creatinine ratio dipstick has a good negative predictive value and a result of < 300mg/g rules out significant proteinuria and avoids unnecessary investigations in pregnancy. Both the visual dipstick (Makromed) and the urinary microalbumin to creatinine ratio dipstick read on the Clinitek 50 system are not accurate when compared to the total 24 hour urinary protein. Differences between the urinary microalbumin to creatinine ratio and 24 hour total urinary protein may be due to the variation in the albumin fraction of the total urinary protein of pre-eclampsia, technical problems with imprecision of the assay technique and clinical causes of false positives and negatives. The improved sensitivity of the automated urinary microalbumin to creatinine ratio dipstick over the visual dipstick suggests it may be a suitable substitute for the visual dipstick in clinical practice Hypertension in pregnancy associated with significant proteinuria is associated with greater adverse maternal and fetal outcome. Outcome of pregnancy is similar when a classification of gestational hypertension is made based either on the 24 hour urinary protein or the urinary microalbumin to creatinine ratio dipstick read on the Clinitek 50 system. The urinary microalbumin to creatinine ratio dipstick is a good screening test to rule out significant proteinuria. It has the potential to improve accuracy of screening for proteinuria and enhancing safety by preventing incorrect diagnosis and unnecessary investigation. Further research is required to determine its full impact and cost effectiveness in the clinical setting. / Thesis (M.Med.)-University of KwaZulu-Natal, 2008.

Thesis (Ph. D.)--Case Western Reserve University, 2005. / Author's name on approval form and OhioLink ETD database: Maria Isabel Rico-Salas. [School of Medicine] Department of Physiology and Biophysics. Includes bibliographical references. Available online via OhioLINK's ETD Center.

Chronic kidney disease is a substantial health problem effecting a large portion of the US population. Presence of excess protein, particularly albumin, in the urine of patients with chronic kidney disease is an independent risk factor for cardiovascular disease and progression to end stage renal disease. In addition, excess protein reabsorption in the proximal tubule is sufficient to cause damage to the proximal tubule independent of the initial condition that lead to chronic disease. In the last decade, excess protein reabsorption by the proximal tubule as a result of chronic kidney damage has been shown to cause oxidative and ER stress, cell death, as well as tubule inflammation and fibrosis in the proximal tubule cell. Only recently have two studies investigated the role of autophagy in protein-induced tubule damage. Autophagy is a dynamic catabolic mechanism used to degrade cytosolic elements in times of cell starvation and is an important process in the cell's response to stress. The results of the studies by Wei Jin Liu et al. and Yamahara et. al. provide important first steps to determine whether autophagy of excess protein in proteinuric states prevents proximal tubule cell toxicity and potentially slow the progression of chronic kidney disease (CKD). This thesis will explore the results of these two studies in the context of proximal tubule damage in chronic kidney disease, and discuss the potential for protein autophagy to improve our understanding and treatment of chronic kidney disease.

Recent large randomized controlled trials (RCTs) have shown that renal revascularization does not confer added benefit to unselected patients with atherosclerotic renovascular disease (ARVD) treated with multi-targeted medical therapy. Results suggest that contemporary medical vascular protection therapy has contributed to improved clinical outcomes in ARVD. However, patients with †̃high-riskâ€TM clinical features have largely been excluded from RCTs and there is consistent observational evidence that this specific patient subgroup may gain benefit from revascularization. Timely identification of these patients through risk stratification and prediction of outcomes post-revascularization remain important challenges. The main aims of this epidemiological research project were to explore how treatment and clinical end-points in ARVD have evolved over the past three decades, to identify the determinants of long-term end-points in ARVD, to investigate the effect of revascularization in a selected †̃high-riskâ€TM subgroup, to investigate novel biomarker association of key end-points and finally to develop a clinical risk prediction model that can aid risk stratification and patient selection for revascularization. These individual studies were all based on a local database that includes details of demographic and clinical data for patients with ARVD referred to our tertiary renal centre between 1986 and 2014. Primary end-point measures included death, progression to end-stage kidney disease, cardiovascular events and a composite end-point composed of the first of any of the above events. Management of ARVD has been influenced by RCT results, leading to a decline in the number of revascularization procedures performed. Traditional cardiovascular risk factors together with baseline renal function and proteinuria are the most important determinants of adverse events in ARVD thus advocating the use of multi-targeted medical therapy and aggressive risk factor control in all patients with ARVD. Nonetheless ARVD is a heterogenous condition and results of this research project show that revascularization can be of benefit in patients with rapidly deteriorating renal function, bilateral severe ARVD and/or < 1g/day baseline proteinuria. A panel of novel biomarkers may have incremental risk predictive value when used in conjunction with more traditional risk factors, and NT-proBNP levels may aid patient selection for revascularization. A simple clinical risk-prediction score based on easily obtainable variables may be used as a bedside tool to help risk stratification and facilitate patient selection for revascularization, thus encouraging a more patient-specific therapeutic approach.

Made available in DSpace on 2014-06-11T19:32:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2003Bitstream added on 2014-06-13T19:03:49Z : No. of bitstreams: 1 guilhen_jc_dr_botfm.pdf: 664786 bytes, checksum: 3ffe505338f83491a511e51efed2c3bd (MD5) / A proteinúria tem sido considerada um sinal importante para identificar o tipo de hipertensão que ocorre na gestação e está relacionada com o resultado materno e perinatal. Objetivo: o objetivo deste estudo foi avaliar, em gestantes hipertensas, por meio da eletroforese, o padrão das proteínas urinárias e seus pesos moleculares. Sujeitos e métodos: eletroforese em gel de poliacrilamida foi realizada em urina de 143 gestantes hipertensas, divididas em quatro grupos: hipertensão arterial crônica (HAC), pré-eclâmpsia/eclâmpsia (PE), hipertensão arterial crônica superposta por pré-eclâmpsia (HAC+PE) e hipertensão gestacional (HG). A presença e o número de bandas das proteínas tubular e glomerular e, seus pesos moleculares foram correlacionados com o tipo de hipertensão arterial, a presença (≥ 300 mg/24horas) ou não de proteinúria, o grau de proteinúria (leve: < 2g/24horas e grave: ≥ 2 g/24horas) e o valor do ácido úrico (< 6 mg% e ≥ 6 mg%). Para comparação das variáveis qualitativas foi usado o teste do qui-quadrado e para comparação das variáveis quantitativas foi usado o teste t de Student. Foi considerado significância quando valor de p < 0,05. Resultados: em todas as gestantes avaliadas foram encontradas proteínas tubular e glomerular e o número de bandas de proteínas não diferenciou os tipos de hipertensão arterial. A presença de pelo menos quatro bandas glomerulares foi significativamente maior nas gestantes com PE e HAC+PE, com proteinúria significativa, com proteinúria grave e com valor de ácido úrico ≥ 6 mg%. Quando comparada com proteínas de peso molecular ≤ 90 kDa a porcentagem de proteínas com peso molecular ≥ 160 kDa foi significativamente maior nas gestantes com PE, HAC+PE e HG, nas gestantes com proteinúria significativa e com ácido úrico ≥ 6 mg%... / Proteinuria has been considered an important sign to identify the hypertensive disorders encountered during pregnancy and it is related to the maternal and perinatal outcomes. Objective: the aim of this study was to evaluate the urinary protein patterns and their molecular weight in hypertensive pregnant women, through urinary electrophoresis. Subjects and methods: Sodium dodecyl sulphatepolyacrylamide gel electrophoresis (SDS-PAGE) was performed on the urine of143 hypertensive pregnant women that were divided into the following groups: chronic hypertension (CH), pre-eclampsia/eclampsia (PE), pre-eclampsia superimposed upon chronic hypertension (CH+PE), and gestational hypertension (GH). Presence and the number of tubular and glomerular protein bands, and their molecular weight were correlated with the type of hypertension, the proteinuria level (present: ≥ 300 mg/24h or absent: < 300 mg/24h; mild: < 2 mg/24h or severe: ≥ 2 mg/24h) and the uric acid level (< 6.0 mg/dL or ≥ 6.0 mg/dL). The chi-square test was used for comparing the qualitative date and the Student t test was used to compare the quantitative date. A p value of 0.05 was regarded as statistically significant. Results: glomerular and tubular proteins were found on all the hypertensive pregnant women and there were no significant differences in the number of protein bands. The glomerular protein band number was significantly higher in PE and CH+PE groups, in pregnant women with proteinuria, in pregnant women with severe proteinuria, and in pregnant women with uric acid level ≥ 6 mg/dL. When compared with the protein of molecular mass ≤90 kDa... (Complete abstract click electronic access below)

O hiperadrenocorticismo é uma das endocrinopatias mais comuns em cães, sendo caracterizado pela exposição excessiva de glicocorticóides secretados pelas adrenais. A hipercortisolemia crônica pode promover várias complicações, incluindo hipertensão sistêmica e glomerulonefrite. A glomerulonefrite pode desencadear variáveis graus de proteinúria e uma tendência de evolução para doença renal crônica. A perda de proteínas na urina, principalmente da albumina, é uma característica das doenças glomerulares e a determinação de variáveis laboratoriais, como a razão proteína:creatinina urinária (RPC), albuminúria (teste de ELISA) e eletroforese das proteínas urinárias, são recomendadas para a elucidação do diagnóstico. Assim, o objetivo do estudo é avaliar a relação entre proteinúria e hipertensão arterial sistêmica em cães com hiperadrenocorticismo e verificar, pela avaliação da albuminúria e do peso molecular das proteínas urinárias, o segmento do néfron que foi comprometido ou lesado. Foram avaliados 30 cães com diagnóstico de hiperadrenocorticismo, subdivididos em 13 cães com hipertensão arterial sistêmica (grupo I) e 17 cães normotensos (grupo II). Foram determinados a razão proteína:creatinina urinária (RPC); a albuminúria pela avaliação da albumina normalizada e razão albumina: creatinina urinária (RAC) e a eletroforese de proteínas pela técnica em gel de poliacrilamida, contendo dodecil sulfato de sódio (SDS - PAGE). Os resultados foram comparados com os dados obtidos de 30 cães clinicamente saudáveis e foi constatado que não houve influência da hipertensão arterial sistêmica nos cães com hiperadrenocorticismo em relação à quantificação da albuminúria, determinada pelo método ELISA, e nem na qualidade e quantidade das bandas de proteínas de baixo (< 60 kDa) e de alto peso molecular (> 60 kDa) determinada pela eletroforese. No entanto foi determinado que cães com hiperadrenocorticismo podem desenvolver lesões glomerulares e tubulares, caracterizadas pela presença de albuminúria e de proteínas de alto e de baixo pesos moleculares, independentemente da presença de hipertensão arterial sistêmica. Concluindo que os métodos laboratoriais, a eletroforese de proteína urinária em gel de poliacrilaminda associada à avaliação quantitativa da proteína total, como a determinação quantitativa da albuminúria, são passíveis de serem empregadas para a avaliação dos segmentos dos néfrons comprometidos que causaram as perdas de proteínas na urina. / Hyperadrenocorticism is a common endocrinopathie in dogs characterized by excessive glucocorticoid expousure secondary to adrenal secretion. Chronic hypercortisolemia may promote several complications, including sistemic hypertension and glomerulonephritis. Glomerulonephritis may lead to different proteinuria degrees and chronic renal disease. Urine protein loss, specially albumin, is characteristic in glomerular diseases. Laboratorial determination by the urinary protein/creatinin ratio (PCR), albuminuria (ELISA test) and urinary protein electrophoresis are recommended for diagnosis. The aim of this study is to evaluate the relationship between proteinuria and sistemic arterial hypertension in dogs with hyperadrenocorticism and to identify the nephron injured segment by evaluating albuminuria and urinary protein molecular weight. Thrithy dogs with hyperadrenocorticism were subdivided in 2 groups as following: 13 dogs with sistemic arterial hypertension (group I) and 17 normal dogs (group II). Urinary protein/creatinin ratio (PCR); albuminuria using the evaluation of normalized albumin and urinary albumin/creatinin ratio (ACR); and protein electrophoresis using polyacrylamide gel with sodium dodecil sulfate (SDS - PAGE) were performed. Results were compared with data of 30 clinically healthy dogs. No influence of sistemic arterial hypertension in dogs with hyperadrenocorticism was noticed in albuminuria magnitude using the ELISA method, nor in the quality and quantity of low (<60 kDa) and high (> 60 kDa) molecular weight bands observed in electrophoresis. However, dogs with hyperadrenocorticism can develop glomerular and tubular lesions, characterized by albuminuria and by the presence of high and low molecular weight proteins in urine independently of sistemic arterial hypertension. Furthermore, urinary protein electrophoresis in polyacrylaminde gel associated to quantitative evaluation of total protein such as the quantitative determination of the albuminuria, may be used in evaluating committed nephrons segments that caused urine protein loss.

O hiperadrenocorticismo é uma das endocrinopatias mais frequentes em cães. As manifestações clínicas e as lesões associadas com o hiperadrenocorticismo resultam primariamente da hipercortisolemia crônica. Várias são as alterações clínicas observadas em diversos sistemas orgânicos, como também as laboratoriais que ocorrem como consequência dos efeitos gliconeogênico, lipolítico, catabólico, protéico e anti-inflamatório dos glicocorticóides. No que concerne aos rins, a hipercortisolemia crônica pode causar lesão do glomérulo, como também esta estrutura pode sér comprometida secundariamente pela hipertensão arterial sistêmica e, assim, evoluir para doença renal crônica. Neste estudo foram avaliados 10 cães normotensos com hiperadrenocorticismo hipófise dependente, antes e após a terapia com trilostano, com o intuito de verificar a existência ou não de proteinúria patológica pelos métodos quantitativos (razão proteína-creatinina urinária) e qualitativos (eletroforese de proteínas urinárias), como também de acompanhar a intensidade da mesma ao longo da evolução da doença e do curso da terapia. A principal lesão renal detectada nos cães com HAC foi no segmento tubular, constatada pelo predomínio de bandas de proteínas urinárias de baixo peso molecular, indicando o comprometimento na absorção dessas proteínas no segmento proximal do néfron, sendo que a presença dessas bandas perduraram ao longo da terapia, mesmo quando as concentrações séricas de cortisol diminuíram gradativamente após a terapia com trilostano. Ainda, o bom controle do hiperadrenocorticismo pela terapia e a pressão arterial sistêmcia dentro dos valores de normalidade podem ter contribuído para a prevenção do desenvolvimento de lesão glomerular. / Hyperadrenocorticism is one of the most common endocrine disorders in dogs. Clinical sings and organs lesions associated with hyperadrenocorticism result primarily from chronic hypercortisolemia. There are several clinical changes observed in different organ systems, as well as laboratory alterations that occur as a result of the effects of gluconeogenic, lipolytic, catabolic, protein and anti-inflammatory glucocorticoids. Regarding to the kidneys, chronic hypercortisolemia can cause damage to the glomerulus, but also that structure may be compromised by secondary hypertension and, thus, evolve into chronic kidney disease. This study evaluated 10 normotensive dogs with pituitary dependent hyperadrenocorticism, before and after therapy with trilostane, in order to verify the existence of pathological proteinuria by quantitative (urinary protein-to-creatipine) and qualitative (urinary protein electrophoresis) methods, and also to monitor its intensity over the course of the disease and therapy. The main renal lesion detected in dogs with hyperadrenocorticism was in the tubular segment, evidenced by the prevalence of urinary protein bands of lower molecular weight, indicating the lack absorption of these proteins in the proximal segment of the nephron. Low molecular weight proteins persisted throughout therapy, even when serum cortisol concentrations gradually decreased after treatment with trilostane. Moreover, good control of hyperadrenocorticism and blood pressure within the normal range may have contributed to the prevention ofthe development of glomerular injury.

IgA nephropathy is the world's most common primary glomerulonephropathy. Recent evidence in a rat model implicated excessive production of oxygen-free radicals in the pathogenesis and suggested that vitamin E-treatment ameliorated progression. We studied this antioxidant therapy on the glomerular filtration rate (GFR), proteinuria and hematuria in biopsy-proven IgA nephropathy in children. The duration of treatment or placebo was 2 years, with vitamin E treatment consisting of 400 IU/day in children weighing <30 kg, and twice that dose for those >30 kg. We measured GFR at entry, midpoint and exit. At baseline and at 4-month intervals after randomization, urinary protein/creatinine ratios and urinalysis were examined. The mixed model procedure with log transformation was used in data analysis to test treatment difference as well as the potential time effect. Fifty-five patients were randomized and 38 completed at least 1 year of follow-up. At entry, the clinical characteristics were not different between the treatment and placebo groups. There was a trend toward better preservation of GFR in vitamin E-treated versus placebo patients, 127±50 vs. 112±31 ml/min/1.73 m2, respectively (P=0.09). The urinary protein/creatinine ratio was significantly lower in the vitamin E-treated group vs. placebo; 0.24±0.38 vs. 0.61±1.37 (P<0.013). However, there was no difference in the prevalence of hematuria between the groups. Vitamin E treatment in our study patients was associated with significantly lower proteinuria, but no effect on hematuria. While there was a trend toward stabilization of GFR in the vitamin E-treated patients, longterm treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function in IgA nephropathy.

Background/objectives The relationship between nonalcoholic fatty liver disease (NAFLD) and albuminuria has been shown in many epidemiologic studies, although the results were inconsistent. This meta-analysis was conducted to summarize all available data and to estimate the risk of albuminuria among patients with NAFLD. Methods Comprehensive literature review was conducted utilizing Medline and Embase database through January 2018 to identify studies that compared the risk of albuminuria among patients with NAFLD versus those without NAFLD. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results Nineteen studies (17 cross-sectional studies and two cohort studies) with 24 804 participants fulfilled the eligibility criteria and were included in this meta-analysis. The risk of albuminuria among patients with NAFLD was significantly higher than those without NAFLD with the pooled odds ratio (OR) of 1.67 [95% confidence interval (CI): 1.32-2.11]. Subgroup analysis demonstrated the significantly increased risk of albuminuria among patients with NAFLD without diabetes with pooled OR of 2.25 (95% CI: 1.65-3.06). However, we found no significant association between albuminuria and NAFLD among diabetic patients [pooled OR 1.28 (95% CI: 0.94-1.75)]. Conclusion A significantly increased risk of albuminuria among patients with NAFLD was observed in this meta-analysis. Physicians should pay more attention to the early detection and subsequent treatment of individuals with microalbuminuria especially in patients with NAFLD.