Establishing equations to evaluate 24 hour urine protein excretion using routine urinalysis.

AIM: It is necessary to screen people at high risk for proteinuria with an economical, reliable and convenient method. The aim of this study is to establish a new approach to predict 24 h urine protein (24 h UP) by routine laboratory assays. METHODS: Five centres were included and a total of 4211 hospitalized patients were enrolled. All samples were assayed for dipstick protein (DSP), specific gravity (SG), 24 h UP and serum albumin (ALB) simultaneously. 4211 patients were randomly divided into two groups for establishing and testing the equations. Equations were built by multiple log-linear regressions. RESULTS: (i) DSP is significantly correlated to 24 h UP in a logarithmic pattern; (ii) SG interprets 24 h UP for specific DSP; (iii) Equation 1 = 0.203 × 10(dummy-variable F) × [100 (SG-1)](-0.470) ; and (iv) Equation 2 = 13.366 × 10(dummy-variable F) × [100 (SG-1)](-0.547) × [ALB (g/L)](-1.130) The dummy-variable F had a point-to-point accordance to DSP (detailed in text). CONCLUSION: Combination of DSP and SG can interpret normal-range proteinuria well, and helped by ALB, their interpretation for macro proteinuria is much improved. It is dependable and economical for routine urinalysis to evaluate pathological proteinuria by equation.

Inhibition of platelet activation could decrease thrombotic events in hemodialysis PF4/H antibody-positive patients.

BACKGROUND: Platelet factor 4/heparin (PF4/H) antibody detection is widely used to evaluate the risk of thrombosis in patients undergoing hemodialysis (HD). Most patients who are PF4/H-antibody-positive can survive thrombosis, but the reason has not been clarified. In addition, no valid preventive methods for thrombosis in patients undergoing HD have been confirmed. METHODS: A single-center, semi-randomized controlled study was designed. In total, 157 patients fulfilled the inclusion criteria and participated. Patients were first divided according to PF4/H antibody detection and then subdivided randomly according to different anti-platelet agent descriptions. RESULTS: (1) PF4/H antibody-positive patients suffered a significantly higher incidence of thrombosis than those who were antibody-negative; (2) PF4/H antibody-positive patients who survived a thrombosis manifested a significantly longer bleeding time and decreased maximum percentage of platelet aggregation inhibition; (3) aspirin and clopidogrel decreased the incidence of thrombosis in PF4/H antibody-positive patients by inhibiting platelet activation. CONCLUSION: The PF4/H antibody was effective for prediction of the risk of thrombosis, except in patients with dysfunctional platelets; aspirin manifested effects similar to clopidogrel in terms of prevention of thromboses in PF4/H antibody-positive patients, but costs much less and is therefore recommended.

A single-center analysis of genotype-phenotype characteristics of Chinese patients with autosomal dominant polycystic kidney disease by targeted exome sequencing.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by PKD1 and PKD2 mutations. However, only a few studies have investigated the genotype and phenotype characteristics of Asian patients with ADPKD. This study aimed to investigate the relationship between the natural course of ADPKD genotype and phenotype. Methods: Genetic studies of PKD1/2 genes of Chinese patients with ADPKD in a single center were performed using targeted exome sequencing and next-generation sequencing on peripheral blood DNA. Results: Among the 140 patients analyzed, 80.00% (n = 112) harbored PKD1 mutations, 11.43% (n = 16) harbored PKD2 mutations, and 8.57% (n = 12) harbored neither PKD1 nor PKD2 mutations. The average age at dialysis was 52.60 ± 11.36, 60.67 ± 5.64, and 52.11 ± 14.63 years, respectively. The renal survival rate of ADPKD patients with PKD1 mutations (77/112) was significantly lower than that of those with PKD2 mutations (9/16), leading to an earlier onset of end-stage renal disease (ESRD). Renal prognosis was poor for those with nonsense mutations, and they required earlier renal replacement therapy. Conclusions: The genotype and phenotype characteristics of ADPKD patients potentially vary across ethnic groups. Our findings supplement the genetic profiles of Chinese ADPKD patients, could serve as a guide for therapy monitoring and prognosis assessment of ADPKD, and may improve the clinical diagnosis.

The Potential Significance of ABO Genotyping for Donor Selection in Kidney Transplantation.

Background: The ABO blood group system is clinically important in kidney transplantation, but ABO genotyping fails to attract sufficient attention in some countries and regions. We identified one case of early graft dysfunction due to an ABO genotype mismatch. Here, we performed ABO genotyping in blood samples, analyzed grouping discrepancies, and investigated the weak A subgroup frequency in kidney transplantation candidates. Methods: Blood samples from 302 uremic patients with grouping discrepancies and 356 uremic patients with type A blood were analyzed using standard serologic serotyping techniques. The ABO genotypes and alleles were analyzed by polymerase chain reaction sequence-specific primer (PCR-SSP) and sequence-based typing (PCR-SBT). Results: All 302 uremic patients with grouping discrepancies carried weak ABO subgroup alleles and 77.48% carried irregular ABO antibodies. The discrepancy rate between serotyping and genotyping was 42.38%, and the mismatching rate of donor selection according to serotype reached 88.74%. And 2.53% of 356 uremic patients with type A blood were determined to be in the weak A subgroup, which was a higher percentage than that observed in the healthy Chinese population (0.53%) by serological screening, but much lower than that observed in Caucasians (20%). Conclusion: We revealed the high risk of blood type misjudgment and genetically ABO-mismatched transplantation if serological test was performed only in blood-group typing. Improved precision of ABO genotyping is crucial for successful kidney transplantation and reasonable organ allocation.

IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study.

The deposition of IgG4 of antibodies against phospholipase A2 receptor (anti-PLA2R) is predominating in the kidneys of patients with idiopathic membranous nephropathy, while its predictive value has not been determined. It was a retrospective study, and 438 patients were included. Serum samples of two time points [before intervention (baseline) and after 1.5-year treatment (endpoint)] were detected for total and IgG4 anti-PLA2R. IgG4 <0.26 RU/mL or total <20 RU/mL was considered as seronegativity. Bi-positivity/bi-negativity was defined when patients'antibodies were found positive or negative both at the baseline and endpoint. Completed remission (CR) was a major clinical outcome. A series of complement ingredients (MASP-1/2, MBL, C3a, C5a, Factor B, Ba, Bb and C5b-9) were measured in the patients of bi-positivity and bi-negativity: (1) meta-analysis based on six papers conducted seropositivity of anti-PLA2R was a useful predictor for achieving CR, but there was a high heterogeneity; (2) there was significant correlation between the baseline and decrease in IgG4 subclass and the achievement of CR; (3) bi-negativity of IgG4 has a high accuracy of predicting CR compared with total antibodies; (4) in patients of bi-positivity, those achieving CR showed lower MASP-1/2, MBL, C3a, C5a, FB, Ba and Bb than patients failing to achieve CR; (5) the titers of endpoint and decrease in Ba and Bb were associated with improvement of 24 h-UP in those of bi-positivity; and (6) the decrease in Ba was a significant factor for achieving CR in those of bi-positivity. Continuous IgG4 negativity was a useful tool to predict the achievement of CR; however, in patients of continuous IgG4 positivity, those with lower activation of lectin and alternative pathways would still more probably achieve CR.

Effectiveness of and risk associated with aspirin therapy in hemodialysis patients with a background of antiplatelet factor 4/heparin complex antibody detection.

BACKGROUND: The optimal prevention measures against hemodialysis (HD)-associated complications, including all-cause thrombotic events and death, are unclear. METHODS: This prospective study was designed to assess the effect of aspirin on prevention of HD-associated complications. Patients were divided into four groups according to platelet factor-4/heparin-complex (PF4/H) antibody detection and aspirin prescription: Group 1, antibody(-)/aspirin(+); Group 2, antibody(-)/aspirin(-); Group 3, antibody(+)/aspirin(+); and Group 4, antibody(+)/aspirin(-). Adverse events were compared among all four groups. Cox hazard regression was performed to analyze the effects of anti-PF4/H antibody and aspirin on thrombosis and death. RESULTS: This study included 648 patients undergoing HD; 142 were positive for anti-PF4/H antibodies, and 229 had received aspirin before enrollment. During the 4-year follow-up period, 138 patients developed thrombosis, and 63 of these events were anti-PF4/H antibody-associated. A total of 112 patients died; 75 died of coronary heart disease (CHD). Group 4 had a significantly higher incidence of total and anti-PF4/H antibody-associated thrombosis events as well as total and CHD-associated death than did the other three groups. Aspirin had a preventive effect against all adverse events in anti-PF4/H antibody-positive patients, but not in antibody-negative patients. Group 1 patients with baseline D-dimer levels of <0.6µg/mL developed more hemorrhagic events than did patients in the other groups. CONCLUSIONS: Aspirin prevention of thrombosis and death in patients undergoing HD might require consideration of the anti-PF4/H antibody status. In antibody-positive individuals, taking aspirin could improve the prognosis and therefore might be recommended. In antibody-negative individuals, prevention was minimal and the bleeding risk was obviously increased; thus, aspirin should be avoided or at least require careful evaluation prior to aspirin treatment.

Hyperuricemia induces endothelial dysfunction via mitochondrial Na+/Ca2+ exchanger-mediated mitochondrial calcium overload.

BACKGROUND: Uric acid (UA) has proven to be a causal agent in endothelial dysfunction in which ROS production plays an important role. Calcium overload in mitochondria can promote the mitochondrial production of ROS. We hypothesize that calcium transduction in mitochondria contributes to UA-induced endothelial dysfunction. METHODS AND RESULTS: We first demonstrated that high concentrations of UA cause endothelial dysfunction, marked by a reduction in eNOS protein expression and NO release in vitro. We further found that a high concentration of UA increased levels of [Ca2+]mito, total intracellular ROS, H2O2, and mitochondrial O2·-, and Δψmito but not the [Ca2+]cyt level. When the mitochondrial calcium channels NCXmito and MCU were blocked by CGP-37157 and Ru360, respectively, the UA-induced increases in the levels of [Ca2+]mito and total intracellular ROS were significantly reduced. Mitochondrial levels of O2·- and Δψmito were reduced by inhibition of NCXmito but not of MCU. Moreover, inhibition of NCXmito, but not of MCU, blocked the UA-induced reductions in eNOS protein expression and NO release. CONCLUSIONS: The increased generation of mitochondrial O2·- induced by a high concentration of UA is triggered by mitochondrial calcium overload and ultimately leads to endothelial dysfunction. In this process, the activation of NCXmito is the major cause of the influx of calcium into mitochondria. Our results provide a new pathophysiological mechanism for UA-induced endothelial dysfunction and may offer a new therapeutic target for clinicians.

Reversible acute kidney injury caused by paroxysmal nocturnal hemoglobinuria.

The authors report a 57-year-old male patient who presented with diarrhea, darkened urine, jaundice and increased blood urea nitrogen and creatinine. Initially, his symptoms, which included hemolytic anemia, acute renal failure and low platelet count, seemed to be caused by renal injuries associated with thrombotic microangiopathy, hemolytic-uremic syndrome in particular. However, a renal biopsy indicated acute tubular necrosis and hemosiderin deposition. A CD55 and CD59 assay, Ham test and sugar-water hemolysis test confirmed the diagnosis of paroxysmal nocturnal hemoglobinuria. After fluid infusion, diuresis and urine alkalization, the patient gradually regained nearly normal renal function. This case illustrates that paroxysmal nocturnal hemoglobinuria may present with acute kidney injury when hemolysis, diarrhea and hemosiderin deposits in the renal tubular epithelial cells and renal tubules are present. Early diagnosis and treatment is crucial to prevent disease progression and irreversible chronic renal failure.