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.

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.

[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.