Systematic review and meta-analysis of preoperative interventions to support the maturation of arteriovenous fistulae in patients with advanced kidney disease.

BACKGROUND: There is great potential to improve outcomes of arteriovenous fistulas (AVFs) by focusing more on the preoperative period of AVF creation. We aim to systematically review the evidence on safety and efficacy of various preoperative interventions that have been tried to improve AVF maturation and success rate. METHODS: We searched five databases: PubMed, Embase, CINAHL, Cochrane Library and King's Fund Library. Experimental studies that investigated the effect of various preoperative interventions to improve AVF outcomes among advanced chronic kidney disease (CKD) patients were searched. The effect size for primary outcome was calculated as the weighted mean difference in the final vessel calibre, rate of AVF maturation or primary failure between the intervention and control arm. We also assessed adverse effects and dropout rates. This review was preregistered in the International Prospective Register of Systematic Reviews (CRD42020193257). RESULTS: Eight eligible studies were identified involving three types of intervention: hand exercise (n = 6), cholecalciferol supplementation (n = 1) and pneumatic compression of the arm using a Fist Assist device (n = 1). The overall effect size of hand exercise on distal cephalic vein calibre was 0.24 mm [95% confidence interval (CI) 0.03-0.45] on meta-analysis of hand exercise studies. On restricting analysis to two randomized controlled trials (RCTs) that had independent control groups, the effect size was higher, at 0.29 mm (95% CI 0.11-0.47). Hand exercise was a well-tolerated intervention, especially when confined to the first 4 weeks. DISCUSSION: Hand exercise is the predominant intervention tried in the preoperative period of AVF creation, although there is methodological heterogeneity. Intermittent pneumatic compression using a Fist Assist device is a novel intervention that has shown some promise. Well-designed prospective RCTs are needed on preoperative interventions among advanced CKD patients, aimed at improving AVF outcomes.

Energy expenditure estimates in chronic kidney disease using a novel physical activity questionnaire.

BACKGROUND: Physical activity (PA) levels are low in patients with advanced chronic kidney disease (CKD), and associate with increased morbidity and mortality. Reliable tools to assess PA in CKD are scarce. We aimed to develop and validate a novel PA questionnaire for use in CKD (CKD-PAQ). METHODS: In Phase 1, a prototype questionnaire was developed based on the validated recent PAQ (RPAQ). Structured feedback on item relevance and clarity was obtained from 40 CKD patients. In Phase 2, the questionnaire was refined in three iterations in a total of 226 CKD patients against 7-day accelerometer and RPAQ measurements. In Phase 3, the definitive CKD-PAQ was compared with RPAQ in 523 CKD patients. RESULTS: In the final iteration of Phase 2, CKD-PAQ data were compared with accelerometer-derived and RPAQ data in 60 patients. Mean daily metabolic equivalent of task (MET) and total energy expenditure (TEE) levels were similar by all methods. Intraclass correlation coefficients showed fair (MET) and good (TEE) agreement between accelerometry and both CKD-PAQ and RPAQ. Agreement between questionnaires was excellent. The mean [standard deviation (SD)] daily MET bias was 0.035 (0.312) for CKD-PAQ and 0.018 (0.326) for RPAQ. The mean (SD) TEE bias was 91 (518) for CKD-PAQ and 44 (548) kcal for RPAQ. Limits of agreement (LOA) were wide for both parameters, with less dispersion of CKD-PAQ values. In Phase 3, agreement between questionnaires was good (MET) and excellent (TEE). Bias of CKD-PAQ-derived mean (SD) daily MET from RPAQ-derived values was 0.031 (0.193), with 95% LOA -0.346 to 0.409. Corresponding mean (SD) values for TEE were 48 (325) and -588 to 685 kcal/day. CKD-PAQ appeared to improve discrimination between low activity groups. CONCLUSIONS: CKD-PAQ performs comparably to the RPAQ though it is shorter, easier to complete, and may better capture low-level activity and improve discrimination between low activity groups.

Ultrasound appearances and histological correlation of native arteriovenous fistula stenoses - A retrospective case series.

The pathophysiology of haemodialysis arteriovenous fistulae (AVF) stenoses is not fully understood. The aim of this study was to perform histology assessment of stenoses in native AVF and compare and correlate the findings between ultrasound and histology. Intimal medial thickness (IMT) was measured on ultrasound where there was measurable neointimal hyperplasia at the site of stenosis and percentage intimal thickening calculated. Ultrasound findings were then compared with histology analysis of AVF stenoses in nine patients. In this small sample, different sonographic appearances and histology were demonstrated. Ultrasound demonstrated stenoses with neointimal hyperplasia and those with no measurable neointimal hyperplasia. Percentage intimal thickening was between 0% and 100%. The histology of the de novo stenoses (where no previous radiological or surgical procedure was performed) demonstrated stenoses with neointimal hyperplasia, no neointimal hyperplasia and neointimal hyperplasia and fibrosis. The histology findings after percutaneous angioplasty (PTA) demonstrated stenoses with neointimal hyperplasia and fibrosis and a stenosis with an acute inflammatory reaction. The findings in this small sample demonstrated that AVF stenoses are not a uniform group as demonstrated by different sonographic and corresponding appearances at histology. Ultrasound appearances of neointimal hyperplasia appear to correlate with neointimal hyperplasia on histology. These findings warrant further investigation and may have implications for treatment strategies.

Beta-glucans in advanced CKD: role in endotoxaemia and inflammation.

BACKGROUND/AIMS: (1-3)-ß-D glucans (BG) are cellular components of yeasts and fungi. Elevated blood levels may be an adjunct in diagnosing invasive fungal infection, though can be high in dialysis patients without fungaemia. BG can also induce false positive signals in endotoxin detection assays (Limulus Amoebocyte Lysate [LAL] assay). We explored the relationship between BG levels, renal impairment, endotoxaemia and inflammation. METHODS: We measured serum BG levels, markers of inflammation and blood endotoxin levels in 20 controls, 20 with stages 1-3 chronic kidney disease (CKD), 20 with stages 4-5 CKD, 15 on peritoneal dialysis (PD) and 60 on haemodialysis (HD). Another 30 patients were studied before and after HD initiation. RESULTS: BG levels increased with advancing CKD, being highest in HD patients, 22% of whom had elevated levels (> 80 pg/ml). Levels increased significantly following HD initiation. Levels also correlated positively with CRP, TNFα, IL-6 levels, independently of CKD stage. Blood endotoxin was detectable by LAL assays in 10-53% of the CKD cohort, being most prevalent in the HD group, and correlating positively with BG levels. Adding BG blocking agent to the assay reduced endotoxin detection confining it to only 5% of HD patients. Levels of inflammatory markers were higher in those with detectable endotoxin - whether false- or true positives. CONCLUSION: BG levels increased with decreasing renal function, being highest in dialysis patients. High BG levels were associated with false positive blood endotoxin signals, and with markers of inflammation, independently of CKD stage. The cause for high BG levels is unknown but could reflect increased gut permeability and altered mononuclear phagocytic system function.

Identification of PKD1 and PKD2 gene variants in a cohort of 125 Asian Indian patients of ADPKD.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) accounts for 2.6% of the patients with chronic kidney disease in India. ADPKD is caused by pathogenic variants in either PKD1 or PKD2 gene. There is no comprehensive genetic data from Indian subcontinent. We aimed to identify the pathogenic variants in the heterogeneous Indian population. PKD1 and PKD2 variants were identified by direct gene sequencing and/or multiplex ligation-dependent probe amplification (MLPA) in 125 unrelated patients of ADPKD. The pathogenic potential of the variants was evaluated computationally and were classified according to ACMG guidelines. Overall 300 variants were observed in PKD1 and PKD2 genes, of which 141 (47%) have been reported previously as benign. The remaining 159 variants were categorized into different classes based on their pathogenicity. Pathogenic variants were observed in 105 (84%) of 125 patients, of which 99 (94.3%) were linked to PKD1 gene and 6 (6.1%) to PKD2 gene. Of 159 variants, 97 were novel variants, of which 43 (44.33%) were pathogenic, and 10 (10.31%) were of uncertain significance. Our data demonstrate the diverse genotypic makeup of single gene disorders in India as compared to the West. These data would be valuable in counseling and further identification of probable donors among the relatives of patients with ADPKD.

Prevalence and outcomes of chronic liver disease in patients receiving dialysis: systematic review and meta-analysis.

Background: Patients receiving dialysis for end-stage kidney disease (ESKD) commonly co-exhibit risk factors for hepatic impairment. This systematic review and meta-analysis aimed to quantify the coexistence of chronic liver disease (CLD) and characterize risk factors and outcomes. Methods: We searched the following databases from inception to May 2021: CINAHL, Cochrane Library, Embase, Kings Fund Library, MEDLINE and PubMed. The protocol was pre-registered on PROSPERO (study ID: CRD42020206486). Studies were assessed against three inclusion criteria: adults (>18 years) with ESKD receiving dialysis, primary outcome involving CLD prevalence and publications in English. Moderator analysis was performed for age, gender, study size and publication year. Sensitivity analysis was performed where applicable by removing outlier results and studies at high risk of bias. Results: Searches yielded 7195 articles; of these 15 met the inclusion criteria. A total of 320 777 patients were included. The prevalence of cirrhosis and non-alcoholic fatty liver disease (NAFLD) was 5% and 55%, respectively. Individuals with CLD had 2-fold higher mortality than those without {odds ratio [OR] 2.19 [95% confidence interval (CI) 1.39-3.45]}. Hepatitis B [OR 13.47 (95% CI 1.37-132.55)] and hepatitis C [OR 7.05 (95% CI 4.00-12.45)], but not diabetes, conferred increased cirrhosis risk. All studies examining NAFLD were judged to be at high risk of bias. We found no data on non-alcoholic steatohepatitis (NASH). Deaths from CLD, cancer and infection were greater among cirrhotic patients. Conclusions: CLD is prevalent in dialysis patients. Hepatitis B and C confer increased risk of CLD. The impact of NAFLD and NASH cirrhosis requires further study. CLD is associated with an increased risk of mortality in this setting.

Pauci-immune crescentic glomerulonephritis associated with metastatic rectal carcinoma.

Paraneoplastic glomerular disease is well recognised, although it most frequently presents with clinical features of the nephrotic syndrome. This case describes a 74-year-old male with metastatic rectal adenocarcinoma treated surgically with anterior resection followed by adjuvant capecitabine chemotherapy. Having previously had normal renal function, he developed an acute kidney injury with active urinary sediment following the discovery of liver metastases. A renal biopsy was performed, which revealed an active crescentic pauci-immune glomerulonephritis. The patient was treated with high dose oral corticosteroids which led to some improvement in renal function, although he was still left with significant kidney impairment, which limited further safe oncological treatment. This case highlights a rare presentation of glomerular disease in the setting of malignancy and also demonstrates the adverse impact that kidney impairment can have on outcomes in patients with cancer.

Management of acute kidney injury in cirrhosis.

Acute kidney injury (AKI) is a relatively frequent problem, occurring in approximately 20 % of hospitalized patients with cirrhosis. Although serum creatinine (S Cr) is the most commonly used method to determine AKI because of easy availability and low cost, practically it underestimates the extent of kidney injury in patients with chronic liver disease. AKI is defined as an abrupt rise in S Cr of 0.3 mg/dl or more (>26.4 mmol/l) or an increase of 150 % or more (1.5-fold) from baseline. The cause of AKI in cirrhosis is multifactorial and is unique in terms of pathogenesis. The most common causes of AKI in cirrhosis can be subdivided into either functional or structural. The functional group includes volume-responsive (prerenal azotemia) and volume-unresponsive states (hepatorenal syndrome). Volume responsive is the most common type of AKI due to frequent use of diuretics, large volume abdominal paracentesis and gastrointestinal bleeding in patients with liver disease. The structural causes include acute tubular necrosis, tubulointerstitial and glomerular diseases. Patients with decompensated cirrhosis are in a vasodilatory state leading to a decrease in effective arterial blood volume, predisposing to AKI. Therefore, management of AKI depends on the underlying cause, and therapy should be directed toward removal of the cause. The outcome in cirrhosis when patients are on dialysis is very dismal. Every effort should be made to prevent AKI.

Iron deficiency masquerading as idiopathic intracranial hypertension.

A 13-year-old female presented with complaints of headache, vomiting, diplopia and progressive blurring of vision developing sequentially over 1 month. Examination revealed marked pallor and bilateral lateral rectus palsy with a visual acuity of 6/12 and 6/36 in the left and the right eye, respectively. Fundus examination showed late stage papilloedema in both eyes. Investigation for anaemia revealed severe iron deficiency. MRI of the brain was normal. The cerebrospinal fluid opening pressure was markedly raised at 320 mm of water but fluid analysis did not reveal any abnormality. Thus, a diagnosis of iron deficiency anaemia with idiopathic intracranial hypertension was made. The patient responded dramatically to intravenous iron treatment. Physicians must be aware of this rare presentation of the common problem of iron deficiency, the rapid correction of which plays an instrumental role in salvaging the patient's vision and preventing a recurrence of disease.