CHOLESTEROL CRYSTAL EMBOLISM: A RECOGNIZABLE CAUSE OF RENAL DISEASE

7openopenFrancesco Scolari; Regina Tardanico; Roberta Zani; Alessandra Pola; Battista Fabio Viola; Ezio Movilli; Rosario MaiorcaScolari, Francesco; Regina, Tardanico; Roberta, Zani; Alessandra, Pola; Battista Fabio, Viola; Ezio, Movilli; Rosario, Maiorc

Supportive treatment for cast nephropathy in patients with multiple myeloma; a pilot study

Introduction: Cast nephropathy is a prevalent cause of acute kidney injury (AKI) in patients with myeloma. Objectives: The aim of this study is to define the outcome of a standardized supportive therapy for cast nephropathy. Patients and Methods: Retrospective analysis of the outcome of cast nephropathy in a University hospital for a period of five years. Data analysed; serum creatinine, estimated glomerular filtration rate (eGFR; mL/min/1.73 m2 BSA) and need for dialysis. Standardized therapy with the aim of preventing/removing tubular casts; fluid administration and mannitol to increase urine flow, sodium bicarbonate to alkalize the urine and low dose steroid to reduce peritubular inflammation. Statistical analysis: Student's t-test or the Mann-Whitney test according to data distribution. A two-tailed P value <0.05 was considered statistically significant. Survival curve was drawn according to Kaplan and Meier. Results: Twenty-seven cases were reviewed. Upon admission, mean serum creatinine was 7.1±4.9 mg/dL and mean eGFR 6±4 mL/min/1.73 m2 BSA; 30% of patients had oligo-anuria. Diagnosis of cast nephropathy was presumptive in 23 patients, and renal biopsy proven in four. Hemodialysis was required by 10 (37%) patients, two of whom continued dialysis after discharge. At discharge, serum creatinine was 3.7±2.5 mg/dL and eGFR 20±13 mL/min/1.73 m2 BSA (P=0.002), and after a median of 3.4 months, the values were 2.9±2.1 mg/dL and 35±32 mL/min/1.73 m2 BSA, respectively. Patient survival was 60% after 24 months. Conclusion: Administration of fluid, mannitol, sodium bicarbonate and low-dose steroid may improve the outcome of cast nephropathy. Despite the fact that the study has many limitations, its findings could be the base for prospective controlled trials on cast nephropathy and could be useful in those countries where the expensive extracorporeal treatments are not available

The Challenge of Diagnosing Atheroembolic Renal Disease

Background— Atheroembolic renal disease (AERD) is caused by showers of cholesterol crystals released by eroded atherosclerotic plaques. Embolization may occur spontaneously or after angiographic/surgical procedures. We sought to determine clinical features and prognostic factors of AERD. Methods and Results— Incident cases of AERD were enrolled at multiple sites and followed up from diagnosis until dialysis and death. Diagnosis was based on clinical suspicion, confirmed by histology or ophthalmoscopy for all spontaneous forms and for most iatrogenic cases. Cox regression was used to model time to dialysis and death as a function of baseline characteristics, AERD presentation (acute/subacute versus chronic renal function decline), and extrarenal manifestations. Three hundred fifty-four subjects were followed up for an average of 2 years. They tended to be male (83%) and elderly (60% >70 years) and to have cardiovascular diseases (90%) and abnormal renal function at baseline (83%). AERD occurred spontaneously in 23.5% of the cases. During the study, 116 patients required dialysis, and 102 died. Baseline comorbidities, ie, reduced renal function, presence of diabetes, history of heart failure, acute/subacute presentation, and gastrointestinal tract involvement, were significant predictors of event occurrence. The risk of dialysis and death was 50% lower among those receiving statins. Conclusions— Clinical features of AERD are identifiable. These make diagnosis possible in most cases. Prognosis is influenced by disease type and severity

Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis

Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis.BackgroundHyperlipemia characterizes nephrotic syndrome (NS) and contributes to the progression of the underlying nephropathy. The data in the literature support an implication of apolipoprotein E (apoE) in both hyperlipemia and focal segmental glomerulosclerosis (FSGS), a malignant condition associated with NS.MethodsThe apoE genotype was determined in 209 nephrotic patients, who were classified according to age and their response to steroids as resistant children (N = 96) and adults (43), and steroid dependent (33) and steroid responder (37) children. A total of 123 presented the histological features of FSGS. In a subgroup of 28 patients, serum and urinary levels of apoE and renal deposits were evaluated by immunofluorescence.ResultsThe allelic frequencies of the three major haplotypes γ2, γ3, and γ4 were the same in nephrotic patients versus controls, and homozygosity for γ3γ3 was comparably the most frequent genotype (70 vs. 71%) followed by γ3γ4, γ2γ3, γ2γ4, γ4γ4. Serum levels of apoE were fivefold higher in NS and in FSGS patients than in controls, with a direct correlation with hypercholesterolemia and proteinuria. ApoE genotypes did not influence serum levels. Urinary levels were 1/10,000 of serum with an increment in nephrotic urines. Finally, immunofluorescence demonstrated the absence of apoE in sclerotic glomeruli, while comparably nephrotic patients with membranous nephropathy had an increased glomerular expression of apoE.ConclusionsApoE is dysregulated in NS with a marked increment in serum, which is a part of the complex lipid metabolism. Down-regulation of glomerular apoE instead is a peculiarity of FSGS and may contribute to the pathogenesis of the disease. The normal distribution of apoE genotypes in nephrotic patients with FSGS excludes a pathogenetic role of genetic variants

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN