Low intracellular water and incident cognitive impairment in chronic hemodialysis patients.

OBJECTIVE: To explore the effect of intracellular water (ICW) evaluated by the bioelectrical Impedance Spectroscopy (BIS) on the risk of incident cognitive impairment (CI) in chronic hemodialysis (HD) patients. METHODS: Three thousand three hundred eighty-five patients were recruited and monitored prospectively for up to 3 years (the median follow-up time, 2 years) in this observational cohort study. Mini-Mental State Examination score (MMSE) was used to assess the global cognitive function. ICW was measured by body composition monitor based on BIS. Multiple Cox regression models, stratified analyses, and interactive analyses were conducted. RESULTS: During the follow-up period, 1256 patients (37.1%) experienced incident CI. The incidence of CI was increased with decreasing quartiles of ICW (27.4%, 32.2%, 38.9%, and 50.1% for the fourth, third, second, and first quartiles, respectively). Decreased ICW was significantly associated with incident CI. The association remained statistically significant even after adjusting for age, sex, education, albumin, C-reactive protein, residual renal function and various medical histories. The hazard ratios were 1.38 (1.17-1.64) and 1.28 (1.08-1.52) for ICW quartile 1 and quartile 2, respectively (reference, quartile 4). The association stably existed across subgroups, and the residual renal function had an interactive role in the association between ICW and incident CI (p = 0.014). CONCLUSION: Low baseline ICW was an independent risk factor for CI in chronic HD patients. Our finding highlights the necessity of using BIS to measure body composition when assessing the risk of CI in HD patients.

Decreased intracellular water is associated with sarcopenic obesity in chronic haemodialysis patients.

OBJECTIVE: To explore the association between intracellular water (ICW) and sarcopenic obesity in patients undergoing chronic haemodialysis (HD). METHODS: A multicentre, cross-sectional study of 3354 adult chronic HD patients was conducted in 20 haemodialysis centres from June 1, 2021, to August 30, 2021. The diagnosis of sarcopenic obesity was made according to the revised Asian Working Group's definition of sarcopenia combined with obesity per the body fat percentage definition. Body composition was evaluated by a body composition monitor using bioimpedance spectroscopy. Multiple logistic regression models, stratified analyses, interactive analyses, and receiver-operating characteristic analyses were conducted. RESULTS: A total of 752 patients were diagnosed with sarcopenic obesity among 3354 participants. The patients were grouped by sex-specific ICW median levels, and the prevalence of sarcopenic obesity was significantly higher in the low ICW group than in the high ICW group (41.3%vs 3.0%). Decreased ICW was significantly associated with sarcopenic obesity. The association remained statistically significant even after adjusting for dialysis vintage, age, body mass index, biochemical indicators, and various medical histories. The odds ratios of the low ICW group were much higher than those of the high ICW group in both males and females (P for trend < 0.001). The association was stable across subgroups, and the interaction analysis showed that age, body mass index and history of diabetes had interactive roles in the association between ICW and sarcopenic obesity (P for interaction < 0.05). Furthermore, the ICW cut-off values for identifying sarcopenic obesity were 19.1 kg and 14.5 kg for males and females, respectively. CONCLUSION: Decreased ICW was an independent risk factor for sarcopenic obesity in chronic HD patients. The measurement of ICW by bioimpedance spectroscopy might be a non-invasive and valid means for identifying the risk of future sarcopenic obesity in HD patients.

A 55-Day-Old Female Infant Infected With 2019 Novel Coronavirus Disease: Presenting With Pneumonia, Liver Injury, and Heart Damage.

BACKGROUND: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were mainly based on information from adult populations. Limited data are available for children with COVID-19, especially for infected infants. METHODS: We report a 55-day-old case with COVID-19 confirmed in China and describe the identification, diagnosis, clinical course, and treatment of the patient, including the disease progression from day 7 to day 11 of illness. RESULTS: This case highlights that children with COVID-19 can also present with multiple organ damage and rapid disease changes. CONCLUSIONS: When managing such infant patients with COVID-19, frequent and careful clinical monitoring is essential.

The treatment and follow-up of 'recurrence' with discharged COVID-19 patients: data from Guizhou, China.

We reported 20 cases of discharged COVID-19 patients whose RT-PCR test results showed 're-positive'. After finding 're-positive', these patients were admitted to hospital for the second time and were followed up until the end of May 2020. We recorded detailed treatment and follow-up process, and collected relevant data. The possible causes and potential clinical significance of this phenomenon are discussed.

Association of Body Composition and Intradialytic Hypotension in Hemodialysis Patients.

BACKGROUND/AIM: The relationship between body mass index (BMI) and intradialytic hypotension (IDH) has been inconsistently reported, but no further research has investigated the correlation between body composition and IDH so far. This study aimed to determine whether the lean tissue index (LTI), fat tissue index (FTI), or both derived from body composition monitoring (BCM) is associated with IDH defined as a nadir intradialytic systolic blood pressure of <90 mm Hg and ≥3 episodes hypotension per 10 hemodialysis (HD) treatments in patients undergoing prevalent HD. METHODS: The observational cohort study comprised 1,463 patients receiving thrice-weekly HD from 13 dialysis centers. LTI and FTI were assessed using a BCM machine, a multifrequency bioimpedance spectroscopy device. Unadjusted and multivariable adjusted logistic regression models were fit to estimate the association of body composition with the odds of developing IDH. RESULTS: One hundred and seven patients (7.3%) were diagnosed as IDH. The difference in dialysis vintage, BMI, FTI, LTI, high-density lipoprotein cholesterol, and C-reactive protein between IDH and non-IDH groups was statistically significant (all p < 0.05). The prevalence of diabetes among IDH patients was slightly higher than among non-IDH patients. In logistic regression models, low LTI and high FTI, but not high BMI were associated with greater odds of IDH ("high" as above median and "low" as below median). When patients were further stratified into 4 distinct body composition groups based on both the LTI and FTI, only the low LTI/high FTI group was connected with a significantly higher odds of IDH (OR 2.686, 95% CI 1.072-6.734; reference: low LTI/low FTI group). CONCLUSIONS: The LTI and FTI can provide better correlation of IDH occurrence than the BMI alone in prevalent HD patients. The low LTI/high FTI appears to be most associated with IDH. An optimal body composition for preventing the occurrence of IDH needs to be determined.

Thymosin ß4 alleviates renal fibrosis and tubular cell apoptosis through TGF-ß pathway inhibition in UUO rat models.

BACKGROUND: Thymosin ß4 (Tß4) is closely associated with the cytoskeleton, inflammation, wound healing, angiogenesis, apoptosis, and myocardial regeneration, but the effects of Tß4 treatment on chronic renal tubular interstitial fibrosis (CRTIF) are poorly known. This study aimed to examine the effects of Tß4 on the renal apoptosis and the expression of transforming growth factor (TGF-ß), E-cadherin, and α-smooth muscle actin (α-SMA) in CRTIF rat models. METHODS: Male SD rats were randomized into four groups (sham group, unilateral ureteral obstruction (UUO) group, UUO + low-dose Tß4 group, and UUO + high-dose Tß4 group). The pathological changes of kidney tissue and its function were assessed two weeks after UUO. In renal interstitial tissue,TGF-ß, E-cadherin and α-SMA expression was detected by western blot. In tubular epithelial cells, E-cadherin and α-SMA expression was detected using Real-time qPCR and western blot. Cell apoptosis of rat renal interstitial tissue and tubular epithelial cells was evaluated by immunofluorescence and western blot. RESULTS: Two weeks after UUO, no differences in blood urea nitrogen and creatinine were observed between the four groups (P > 0.05). Compared to the UUO group, Tß4 treatment decreased the 24-h proteinuria (P < 0.001) and reduced the area of pathological change (P < 0.01); this effect was more apparent in the UUO + high-dose Tß4 group. Compared to the UUO group, a significant decrease in TGF-ß and α-SMA protein expression was observed in the high-dose Tß4 group. The level of E-cadherin protein was lower in the UUO group than the Tß4 groups, and high-dose Tß4 treatment further increased E-cadherin expression and improved cell apoptosis in the renal interstitial tissue. Analysis of in vitro tubular epithelial cells showed that α-SMA mRNA and protein expression decreased, while E-cadherin mRNA and protein expression increased by Tß4 treatment. Similarly, these changes were more significant in the UUO + high-dose Tß4 group. Tß4 treatment improved the apoptosis of In vitro tubular epithelial cells compared with pure TGF-ß stimulation, and equally, the decrease of apoptosis was more apparent in the TGF-ß + high-dose Tß4 group. CONCLUSIONS: Tß4 treatment might alleviate the renal fibrosis and apoptosis of tubular epithelial cells through TGF-ß pathway inhibition in UUO rats with CRTIF.

Efficacy and safety of perioperative sodium bicarbonate therapy for cardiac surgery-associated acute kidney injury: a meta-analysis.

OBJECTIVE: Urinary alkalinization with sodium bicarbonate infusion can theoretically protect against the mechanisms of acute kidney injury (AKI). Controversy exists regarding whether sodium bicarbonate infusion can reduce the incidence of AKI from cardiac surgery. A meta-analysis was conducted to show the efficacy and safety of perioperative sodium bicarbonate use for preventing AKI in patients undergoing cardiac surgery. DATA SOURCES: PubMed, CBM, EMBASE, CENTRAL, and Cochrane renal group specialized register were searched for pertinent studies. STUDY SELECTION: Randomized controlled trails and prospective observational cohort studies that compared sodium bicarbonate with sodium chloride or blank control in cardiac surgery with cardiopulmonary bypass were included. Exclusion criteria were duplicate publications, nonadult studies, oral administration of sodium bicarbonate, retrospective analyses, and studies with small sample size (n < 50) or with no data on AKI. DATA EXTRACTION: Study end points, study design, population, operation information, and sodium bicarbonate doses were extracted. DATA SYNTHESIS: Data from 1673 patients in 5 randomized trials and 1 prospective observational cohort study were analyzed. The analysis showed that sodium bicarbonate did not reduce the incidence of postoperative AKI and the need for renal replacement therapy. Postoperative ventilation time, hospital length of stay, hospital death, and mortality within 90 days had no statistical difference between 2 groups. Time in intensive care unit was even slightly longer in the experimental group. CONCLUSIONS: Urinary alkalinization using sodium bicarbonate infusion failed to reduce the incidence rate of AKI or other outcomes in patients undergoing cardiac surgery. This intervention might even prolong intensive care unit stay.

Monocyte-to-lymphocyte ratio and gastrointestinal disorder-related hospitalization in patients on maintenance hemodialysis.

INTRODUCTION: To explore the association between monocyte-to-lymphocyte ratio (MLR) and the risk of hospitalization due to gastrointestinal (GI) disorder in hemodialysis (HD) patients. METHODS: In this multicenter, observational cohort study, 1626 patients were enrolled in 2019 and followed up to 2 years. Cox regression models were performed to estimate the association of MLR with GI disorder-related hospitalization risk. Receiver-operating characteristic (ROC) analyses were conducted to evaluate the cutoff value of MLR in identifying GI disorder-related hospitalization. RESULTS: During a median follow-up of 24 months, GI disorder-related hospitalization occurred in 107 patients. Higher MLR was independently associated with greater risks of GI disorder-related hospitalization. Furthermore, a cut-off value of 0.42 differentiated patients with GI disorder-related hospitalization from those without GI involvement. CONCLUSION: MLR was associated with the occurrence of GI disorder-related hospitalization in HD patients. The blood MLR could be monitored as a useful marker to predict GI disorder-related hospitalization.

[Genetic and clinical study of three Chinese pedigrees with Fabry disease].

OBJECTIVE: Fabry disease is a rare lysosome storage disease featuring X-linked recessive inheritance. The study was to explore potential mutations of alpha-galactosidase A (GLA) gene and their correlation with clinic manifestations in three Chinese pedigrees with Fabry disease. METHODS: All exons and flanking sequences of GLA gene were amplified with PCR. Potential mutations were detected with bidirectional DNA sequencing. Correlation between particular mutations and clinic features were analyzed. RESULTS: A unreported missense mutation, c.797A>C (D266A) in GLA exon 5 was identified in pedigree 1. Also in exon 5, a missense mutation c.644A>G (N215S) was found in pedigree 2. In pedigree 3, a nonsense mutation c.355C>T (Q119X) was found in exon 2. The c.797A>C mutation was not detected in 200 unrelated male controls. The probands of pedigrees 1 and 3 had presented mainly with skin damage and chronic renal insufficiency, whilst the proband of pedigree 2 had presented with hypertrophic cardiomyopathy. CONCLUSION: The unreported c.797A>C (D266A) mutation is the sixth missense type mutation of the 266th codon of GLA gene, and all other 5 missense mutations reported previously had been confirmed to be responsible for Fabry disease. The c.797A>C mutation, not found in 200 unrelated male controls, may be the causative mutation in pedigree 1. The c.644A>G and c.355C>T mutations were first detected in Chinese patients. Variable phenotypes of Fabry disease may be in part attributed to the natures of particular mutations of GLA gene.

Decreased Intracellular to Total Body Water Ratio and Depressive Symptoms in Patients with Maintenance Hemodialysis.

Objective: Depression is a common psychiatric disorder and related to poor outcomes in patients undergoing maintenance hemodialysis (MHD). Previous studies have reported some associations between sarcopenia and depressive symptoms. Recently, intracellular water (ICW) and total body water (TBW) have been found to reflect muscle function and muscle mass. ICW/TBW ratio is a marker of sarcopenia that is simple to assess. However, the relationship between ICW/TBW ratio and depression has not been explored in MHD patients. Methods: In our cross-sectional and multi-center study, 3300 adult MHD patients were included from June 1, 2021, to August 30, 2021. Depressive symptoms were evaluated using the Beck Depression Inventory-II (BDI-II). TBW and ICW were measured by Body Composition Monitor (BCM). Multivariable logistic regression, stratified analyses, and interactive analyses were conducted to assess the relationship between ICW/TBW ratio and depression. Results: About 16.5% of the 3300 MHD patients were found to have depressive symptoms. The prevalence of depression increased with decreasing quartiles of ICW/TBW ratios, and decreased ICW/TBW ratio was independently associated with depression after adjusting for potential confounders. Patients in Quartile 1 of ICW/TBW ratios were more likely to have depressive symptoms (odds ratio 1.55, 95% confidence interval 1.07-2.22; p=0.002) than those in Quartile 4. History of diabetes and education status had interactive roles in the relationship between depression and ICW/TBW ratios (p < 0.05). The association of ICW/TBW ratios and depression existed in patients of both genders and different education levels, but only in non-diabetic patients. Conclusion: In MHD patients, the decreased ratio of ICW/TBW was independently related to high depression rates.

Lean-to-fat tissue ratio as a risk factor for cognitive impairment in patients undergoing maintenance hemodialysis.

OBJECTIVE: The relationship between body mass index (BMI) and cognitive impairment (CI) remains controversial, and no research has been done to explore the effect of lean-to-fat (L/F) tissue ratio on the risk of CI in patients undergoing maintenance hemodialysis (MHD) so far. This study aimed to explore the effect of L/F tissue ratio on the risk of incident CI in patients undergoing MHD. METHODS: In this observational cohort study, 3356 patients were recruited and followed up for a median of 2 years. Global cognitive function was measured using Mini-Mental State Examination score. Lean tissue mass (LTM) and fat tissue mass (FTM) were analyzed using body composition monitor based on bioimpedance spectroscopy (BCM-BIS), and L/F tissue ratio was calculated by LTM divided by FTM. Hazard ratios (HRs) for incident CI were determined by Cox regression. RESULTS: The median age of the cohort was 55 years, and 68.7% patients were less educated. During the follow-up period, 1249 patients (37.2%) experienced incident CI. Patients with lower L/F tissue ratios had significantly higher risks of CI (HR 1.51, 95% confidence interval 1.24-1.84; p < 0.001) than those with higher L/F tissue ratios. The association between L/F tissue ratio and incident CI persisted in all subgroups stratified by sex, age, education status, especially in older and less educated participants. Both in all our patients and subgroups, BMI and CI occurrence were not independently relevant. CONCLUSION: The L/F tissue ratio rather than BMI was an independent risk factor of incident cognitive impairment in patients undergoing MHD.

Sex Differences in the Association of Weight-Adjusted-Waist Index with Sarcopenic Obesity: A Cross-Sectional Study of Hemodialysis Patients.

Objective: To explore the association between weight-adjusted-waist index (WWI) and sarcopenic obesity (SO) in patients with maintenance hemodialysis (MHD). Methods: A multicenter, cross-sectional study that included 3311 adult MHD patients was conducted in 20 hemodialysis (HD) centers from June 1, 2021, to August 30, 2021. Body composition was evaluated by body composition monitor based on bioimpedance spectroscopy. Hand grip strength was measured by CAMRY® dynamometer. WWI was calculated as waist circumference (cm) divided by the square root of body weight (kg). Multiple logistic regression models, spearman correlation analysis, and receiver-operating characteristic (ROC) analyses were conducted. Results: The median age of the study was 55 years, and 39.4% of patients were female. The prevalence of SO was 22.7% in the total population, and patients with SO had higher WWI. Higher WWI quartiles were independently associated with a higher risk of SO in men after adjusting for potential confounders, including age, dialysis vintage, body mass index, biochemical indicators, and various medical histories; the odds ratio (OR) of SO was highest in the fourth quartile of the WWI (OR: 4.08, 95% confidence interval: 2.65-6.27, P for trend <0.001). Age-adjusted WWI provided a better diagnostic power than WWI only for SO in men (area under the ROC curve: 0.72 vs. 0.68, P < 0.001). WWI was not associated with SO in female HD patients. Conclusion: WWI is independently associated with SO in male but not female MHD patients. This anthropometric index is simple to calculate, making it applicable in clinical practice.

Low Lean Tissue Index and Muscle Strength Combined with High Fat Tissue Index Are Associated with Cardiovascular Disease-Related Hospitalisation in Patients on Haemodialysis.

INTRODUCTION: The combined clinical impact of muscle mass, muscle function, and adipose mass on hospitalisation events, especially those that have exact causes, such as cardiovascular diseases (CVDs), had been rarely studied in patients on haemodialysis (HD). This study aimed to determine the influence of lean tissue index (LTI), fat tissue index (FTI), and hand grip strength (HGS) on the risk of CVD-related hospitalisation in patients undergoing chronic HD. METHODS: This multi-centre observational study enrolled a total of 2,041 clinically stable patients aged >18 years and who had undergone HD for at least 3 months at 17 HD units in 2019. The follow-up period was up to 2 years. LTI and FTI were assessed using a body composition monitoring machine, and HGS was measured by a CAMRY® dynamometer. Cox regression models were fit to estimate the associations of body composition and HGS with CVD-related hospitalisation risk. RESULTS: During a mean follow-up of 22.6 months, CVD-related hospitalisation occurred in 492 patients. Compared with the non-CVD group, patients with CVD-related hospitalisation were older; had lower diastolic blood pressure; were more likely to have a history of diabetes; had worse activity status scores and lower levels of LTI, HGS, serum uric acid, and serum creatinine; and had higher FTI levels, body mass index, and extracellular water/intracellular water ratio. In the Cox regression models, low LTI and high FTI were independently associated with CVD-related hospitalisation in both men and women. In men, low HGS was an independent risk factor for CVD-related hospitalisation. When patients were further stratified into four distinct groups according to the sex-specific median values of LTI and FTI, the combination of low LTI and high FTI was an independent risk factor for CVD-related hospitalization (hazard ratio [HR] = 1.79 in men, 95% confidence interval 1.26-2.55; HR = 2.48 in women, 95% confidence interval 1.66-3.71; reference: high LTI/low FTI group). CONCLUSIONS: Among patients on chronic HD, low LTI, and high FTI were associated with CVD-related hospitalisation in men and women, whereas HGS was an independent risk factor for CVD-related hospitalisation in men but not in women. Combining low LTI and high FTI increased the association with hospitalisation risk and was an independent predictor of CVD-related hospitalisation.

Study on Correlation between Body Cell Mass Index and Cognitive Impairment in Hemodialysis Maintaining Patients: A Cross-Sectional Study.

Objective: To investigate the relationship between body cell mass index (BCMI) and cognitive impairment in maintaining hemodialysis (MHD) patients. Methods: We collected the general materials, laboratory indexes, and physical measurement indexes of patients undergoing maintenance hemodialysis in hemodialysis centers of 20 tertiary and tertiary general hospitals in Guizhou Province from June to September 2020. The body composition was measured by bioelectrical impedance method, and the BCMI value was calculated. The subjects were divided into normal cognitive function group (score ≥27), mild cognitive impairment group (score 23-26), and severe cognitive impairment group (score <23). Two groups of people with normal cognitive function and cognitive impairment with similar baseline data (gender, age, and education) were obtained by propensity score matching (PSM). Results: A total of 2008 subjects were included in this study, including 467 cases (23.3%) in the cognitive impairment group. A total of 814 cases were accurately matched after PSM. Multivariate logistic regression analysis showed that the incidence risk of the BCMI Q1 group was 8.99 times higher than that of the Q4 group (95% CI: 5.74 ∼ 14.09, P < 0.001). ROC curve analysis showed that the best threshold of BCMI for predicting cognitive impairment in MHD patients was 9.05, the sensitivity and specificity were 71.5% and 62.7%, respectively, and the area under the curve was 0.713 (95% CI: 0.678 ∼ 0.748, P < 0.001). Conclusions: BCMI is related to cognitive impairment in MHD patients and has predictive value for the onset of cognitive impairment in MHD patients.

The combined therapy of a traditional Chinese medicine formula and Western medicine for a critically ill case infected with COVID-19.

OBJECTIVE: Presentation of a case illustrating the benefits of traditional Chinese medicine (TCM) for treatment of Coronavirus disease 2019 (COVID-19) in critically ill patients. CLINICAL FEATURES AND OUTCOME: A 58-year-old woman presented with cough, fever, dizziness, chest tightness, polypnea and poor appetite. She was admitted to Guizhou Provincial People's hospital, and diagnosed with critically ill type of COVID-19 in February 2020. According to the patient's symptoms and signs, the TCM syndrome differentiation was qi deficiency, dampness-stasis and toxin accumulation. Then she received the combined therapy of a modified Chinese herbal formula and Western medicine. During a twelve-day period of treatment, her respiratory distress and appetite quickly improved. Abnormal laboratory indicators were resumed in time and lung lesions in CT scan largely absorbed. No side effects associated with this Chinese herbal formula were found. Before discharge, two consecutive nasopharyngeal swabs were shown to be negative for severe acute respiratory coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Our case report suggests that collaborative treatments with traditional Chinese medicine prove beneficial in the management of COVID-19 in critically ill patients. In order to give optimal care for this COVID-19 crisis for the whole world, Chinese medicine practitioners and Western medical doctors should work together in frontline.

Efficacy and safety of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in diabetic nephropathy: a meta-analysis.

OBJECTIVE: Pentoxifylline (PTF) has anti-inflammatory properties, which may be beneficial for diabetic nephropathy (DN). A meta-analysis was conducted to assess the additive effect of pentoxifylline and its safety among patients with type 2 DN under blockade of angiotensin system. DATA SOURCES: Relevant studies were searched from PubMed, CBM, EMBASE, CENTRAL and Cochrane renal group specialized register. SELECTION CRITERIA: All RCTs that compared the benefits and harms of pentoxifylline and ACEI/ARB with ACEI/ARB alone for DN were included. DATA EXTRACTION AND ANALYSIS: Pertinent data were extracted independently by two authors. Meta-analyses were performed when more than one study provided data on a comparable outcome. Standard mean differences (SMDs) for proteinuria and albuminuria, mean differences (MDs) for systolic blood pressure (SBP), diastolic blood pressure (DBP), HbA1c, serum creatinine (Scr), creatinine clearance (CrCl) and urine tumor necrosis factor-alpha (UTNF-α), 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I (2) test. Adverse effects were assessed using descriptive techniques. RESULTS: Eight studies including 587 patients with a median duration of 5 months were identified. Compared with ACEI/ARB alone, the combination of PTF and ACEI/ARB significantly reduced proteinuria (SMD 0.76, 95% CI 0.52-0.99), albuminuria (SMD 0.36, 95% CI 0.12-0.59) and UTNF-α (MD 1.56 ng/g, 95% CI 0.09-3.03). However, no statistically significant changes were observed for SBP, DBP, HbA1c, Scr and CrCl. The most frequent adverse effects in patients treated with PTF were gastrointestinal symptoms (28/298) and dizziness (7/298), but in most cases, these symptoms were mild, only six participants withdrew due to intractable nausea and vomiting. CONCLUSIONS: Pentoxifylline can significantly provide additive antiproteinuric effect independent from the decrease in BP or improvement in glycemic control in DN patients under blockade of angiotensin system. Further large, multicenter, high-quality studies with long duration are necessary to prove whether it really has renoprotective effects in this patient population.