Integrating vascular access surveillance with clinical monitoring for stenosis prediction.

BACKGROUND: Arteriovenous fistula and arteriovenous graft are the most common types of vascular access for dialysis; stenosis and thrombosis are major complications leading to access failure and to an incresed risk of mortality. The aim of the present study was to assess the results of integrating  strict vascular access blood flow surveillance with routine clinical monitoring for predicting vascular access stenosis in chronic hemodialysis patients. METHODS: In this retrospective study, chronic dialysis patients with arteriovenous fistula or arteriovenous graft were included from a setting in which all patients underwent quarterly blood flow surveillance in 2017. The results of blood flow surveillance were confirmed by thorough physical examination. Predictive performance of blood flow surveillance models in detecting stenosis in patients with arteriovenous fistula or arteriovenous graft was evaluated. The predictive performance of the quarterly blood flow surveillance model was described by confusion matrix. Differences in accuracy, positive predictive value (PPV), and negative predictive value (NPV) between blood flow surveillance models with distinct blood flow thresholds were evaluated. RESULTS: Of 397 included patients, 336 had an arteriovenous fistula and 61 had an arteriovenous graft. In 2017, 106 percutaneous transluminal angioplasty procedures were performed in patients with an arteriovenous fistula, and 63 in patients with an arteriovenous graft. The results revealed similar predictive performance of surveillance models using an absolute blood flow threshold of < 500 or < 400 mL/min in predicting stenosis in patients with arteriovenous fistula. Blood flow surveillance models for patients with an arteriovenous fistula had significantly higher accuracy than those for patients with an arteriovenous graft. Furthermore, the use of a relative threshold, defined as blood flow < 1000 mL/min and a 25% decline in blood flow, did not affect the predictive performance of blood flow surveillance models. CONCLUSION: Blood flow surveillance models using thresholds of < 400 and < 600 mL/min, followed by thorough physical examination, showed an accuracy of 91.54% and 72.15% in predicting stenosis in patients with arteriovenous fistula and arteriovenous graft, respectively. These two blood flow surveillance models may be integrated with routine clinical monitoring to improve early detection and treatment of stenosis in hemodialysis patients.

Long-Term Effectiveness of Cilostazol in Patients with Hemodialysis with Peripheral Artery Disease.

AIM: The aim of this study was to investigate the effects of continuous cilostazol use on emergency department (ED) visits, hospitalizations, and vascular outcomes in patients with hemodialysis (HD) with peripheral artery disease (PAD). METHODS: This retrospective cohort study recruited 558 adult patients, who had received chronic HD for at least 90 days between January 1, 2008 and December 31, 2012, from the National Health Insurance Research Database. Eligible patients were divided into two groups based on continuing or discontinuing cilostazol treatment. Outcome measures were ED visits, hospitalizations, mortality, and vascular outcomes such as percutaneous transluminal angioplasty, surgical bypass, lower leg amputation, ischemic stroke, hemorrhagic stroke, and cardiovascular events. RESULTS: Patients with continuous cilostazol use had significantly higher prevalence of stroke, cancer, vintage, and the use of angiotensin receptor blocker and ß-blocker, but significantly lower incidence of ischemic stroke and cardiovascular events, as well as lower mortality, than those without continuous cilostazol use (all p＜.05). Continuous cilostazol use was independently associated with lower risk of ED visits, hemorrhagic stroke, and cardiovascular events (adjusted hazard ratios: 0.79, 0.29, and 0.67; 95% confidence intervals: 0.62-0.98, 0.10-0.84, and 0.48-0.96, respectively; all p＜.05). Continuous cilostazol use was significantly associated with higher ED visit-free and cardiovascular event-free rates (log-rank test; p＜.05). CONCLUSION: Continuous treatment of cilostazol in patients with HD with PAD significantly decreases the risk of ED visits, hemorrhagic stroke, and cardiovascular events and improves ED visit-free and cardiovascular event-free rates during long-term follow-up.

Factors affecting arteriovenous access patency after percutaneous transluminal angioplasty in chronic haemodialysis patients under vascular access monitoring and surveillance: a single-centre observational study.

OBJECTIVES: Maintenance of vascular access (VA) patency after percutaneous transluminal angioplasty (PTA) is important and remains a challenge despite VA monitoring and surveillance. The aim of this study was to examine factors affecting the post-PTA arteriovenous access (AVA) patency in patients who have been on close VA monitoring and surveillance for access flow. DESIGN: Retrospective cohort study. SETTING: A single medical centre in Taiwan. PARTICIPANTS: Records of patients who received chronic haemodialysis between 1 January 2017 and 31 December 2018 were retrospectively reviewed. Patients were divided into two groups (without or with PTA intervention on AVA). PRIMARY AND SECONDARY OUTCOME: Patients were followed until reintervention PTA, termination or abandoned VA or end of study. In addition to routine monitoring, VA flow surveillance was performed every 3 months for detection of VA dysfunction adhering to Kidney Disease Outcomes Quality Initiative guidelines. RESULTS: A total of 508 patients were selected for study inclusion (with PTA, n=231; without PTA, n=277). At baseline, variables that differed between groups included malignancy and levels of albumin, uric acid, potassium, phosphorous, high-density lipoprotein, total bilirubin and ferritin (all p<0.05). Significant between-group differences were observed for ß-adrenergic blocking agents (with PTA, 49.8%; without PTA, 37.5%; p, 0.007) and ADP inhibitors (with PTA, 23.8%; without PTA, 11.2%; p<0.001). Among patients with PTA, those with acute myocardial infarction, high ferritin level or arteriovenous graft (AVG) had a significantly higher risk of reintervention post-PTA (p<0.05). Dipeptidyl peptidase-4 inhibitors, thiazolidinediones, ADP inhibitors, and warfarin use were predictors of post-PTA patency (p<0.05). CONCLUSIONS: AVG access type, acute myocardial infarction, and high ferritin levels are risk factors for re-intervention post-PTA. These findings may be useful in the development of prophylactic strategies for monitoring VA function and tailoring surveillance programs for these dialysis patients.

Epidemiology of dermatologic disease in Palau: a cross-sectional study in the national public and community health service.

BACKGROUND: Dermatologic disease is a neglected public health challenge that disproportionately affects resource-poor settings. Globally, dermatologic disease contributes the fourth highest burden of nonfatal disability with the most acute impact in the Oceanic region, including the Republic of Palau. Efforts to address the dermatologic health inequality are hindered without the necessary epidemiologic evidence to guide health policy in the resource-poor setting of Palau. METHODS: We conducted a 4-year cross-sectional study of all Dermatology Service patients in the Belau National Hospital and outreach community health centers from 2015 to 2018. No other specialized dermatology service was available. Skin disease was classified by both diagnosis and Global Burden of Disease criteria and analyzed by age, gender, region, and surrounding Oceanic nations. RESULTS: The study enrolled 494 patients comprising 179 males and 315 females between 2015 and 2018. The most prevalent diseases were eczema (48.8%), superficial fungal infection (24.5%), and pruritus (22.7%). The neglected tropical disease of scabies was detected in four patients. Males were significantly more likely to present with cellulitis, keratinocyte carcinoma, stasis dermatitis, wounds, marine-related dermatitis, viral skin disease, tinea faciei, verruca, and xerosis and females with melasma and hyperpigmentation. CONCLUSION: This study presents the first primary epidemiologic data describing the prevalence of dermatologic disease in the Palauan adult population. The significant burden of disease in Palau compared with other Oceanic nations validates ongoing dermatology services and informs public health implications for resource allocation and disease management to achieve health equality in the resource-poor nation.

Outcomes of the Gore Excluder abdominal aortic aneurysm leg endoprosthesis for treatment of central vein stenosis or occlusion in patients with chronic hemodialysis.

OBJECTIVE: Central venous occlusive disease is a critical complication in long-term hemodialysis patients with arteriovenous (AV) dialysis circuits. The purpose of this retrospective, single-arm cohort study was to evaluate the effectiveness of an abdominal aortic aneurysm (AAA) contralateral leg endoprosthesis to treat symptomatic central venous occlusive diseases in patients with chronic hemodialysis. METHODS: A prospective cohort study included 60 patients on hemodialysis presenting with central venous stenosis or occlusion, who were treated with a Gore Excluder AAA contralateral leg stent graft between December 2013 and July 2018. Follow-up angiography was obtained at 3, 6, and 12 months. The outcomes and duration of primary circuit and target site patency were measured from the time of the stent graft implantation to the first reintervention for AV circuit dysfunction and target site restenosis. Secondary patency was calculated from stent graft implantation to the point when AV access was no longer attainable. RESULTS: Circuit primary patency rate was 54.9% at 1 year of Gore Excluder AAA contralateral leg or iliac extender stent grafts, implanted in 60 hemodialysis patients with central vein occlusive disease. Cumulative target site primary patency rate was 88.3% at 1 year. Secondary patency rate was 95% during follow-up. Patients with concomitant lesions had a significantly higher risk of circuit primary patency dysfunction. CONCLUSIONS: Treatment of central vein obstructions in hemodialysis patients with stent grafts has been appealing owing to the tapered shape with a larger diameter and the availability of various lengths.

Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis.

BACKGROUND: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca2+-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive. METHODS: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) and biopsy-proven acute tubular necrosis (ATN) and followed them up for more than three months. The subjects were divided into high- and low-renal-tubular-TRPA1-expression groups for the comparison of the total recovery of renal function and mortality within three months. The significance of TRPA1 in patient prognosis was evaluated using Kaplan-Meier curves and logistic regression analysis. RESULTS: Of the 46 adult AKI patients with ATN, 12 totally recovered renal function. The expression level of tubular TRPA1 was detected by quantitative analysis of the immunohistochemistry of biopsy specimens from ATN patients. The AKI patients with high tubular TRPA1 expression showed a high incidence of nontotal renal function recovery than those with low tubular TRPA1 expression (OR = 7.14; 95%CI 1.35-37.75; p = 0.02). High TRPA1 expression was independently associated with nontotal recovery of renal function (adjusted OR = 6.86; 95%CI 1.26-37.27; p = 0.03). CONCLUSION: High tubular TRPA1 expression was associated with the nontotal recovery of renal function. Further mechanistic studies are warranted.

Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword?

Given advancements in cancer immunity, cancer treatment has gained breakthrough developments. Immune checkpoint inhibitors, such as programmed cell death 1 (PD-1) inhibitors, are the most promising drugs in the field and have been approved to treat various types of cancer, such as metastatic melanoma, head and neck squamous cell carcinoma, and urothelial carcinoma. However, whether PD-1 inhibitors should be administered to renal transplant patients with advanced cancer remains unclear because the T-cells produced after administration of these inhibitors act against not only tumor antigens but also donor alloantigens. Thus, the use of PD-1 inhibitors in kidney-transplanted patients with advanced cancer is limited on account of the high risk of graft failure due to acute rejection. Hence, finding optimal treatment regimens to enhance the tumor-specific T-cell response and decrease T-cell-mediated alloreactivity after administration of a PD-1 inhibitor is necessary. Thus far, no recommendations for the use of PD-1 inhibitors to treat cancer in renal transplant patients are yet available, and very few cases reporting kidney-transplanted patients treated with PD-1 inhibitors are available in the literature. Therefore, in this work, we review the published cases and suggest feasible approaches for renal transplant patients with advanced malignancy treated by a PD-1 inhibitor. Of the 22 cases we obtained, four patients maintained intact grafts without tumor progression after treatment with a PD-1 inhibitor. Among these patients, one maintained steroid dose before initiation of anti-PD1, two received immunosuppressive regimens with low-dose steroid and calcineurin inhibitor (CNI)-elimination with sirolimus before initiation of anti-PD-1 therapy, and one received combined anti-PD-1, anti-vascular endothelial growth factor (VEGF), and chemotherapy with unchanged immunosuppressive regimens. mammalian target of rapamycin (mTOR) inhibitors and anti-VEGF may act as regulators of tumor-specific and allogenic T-cells. However, more studies are necessary to explore the optimal therapy and ensure the safety and efficacy of PD-1 inhibitors in kidney-transplanted patients.

Association of early loss of primary functional patency of arteriovenous access with mortality in incident hemodialysis patients: A nationwide population-based observational study.

The long-term survival and life quality of hemodialysis (HD) patients depend on adequacy of dialysis via a well-functioning vascular access. Loss of primary functional patency (PFP) of an arteriovenous access (AVA) eventually happens in HD patients. The association between time to loss of PFP of AVAs and mortality in HD patients remains unclear. The retrospective nationwide population-based cohort study compared the hazards of mortality with time to loss of PFP. We enrolled 1618 adult incident HD patients who received HD via AVAs for at least 90 days between January 1, 2001 and December 31, 2013. They were divided into early (≤1 year) and late (>1 year) loss of PFP according to intervention-free intervals (time from first successful cannulation to percutaneous transluminal angioplasty [PTA]). Patients with early loss of PFP were older; had more clinic visits annually and higher Charlson comorbidity index scores; were associated with higher proportions of diabetes mellitus, coronary artery disease, heart failure, stroke, chronic obstructive pulmonary disease, cancer, and use of arteriovenous graft, diuretic, antidiabetic drugs, and aspirin (all P < .05). Kaplan-Meier analysis revealed the cumulative incidence of mortality was significantly higher in patients with early loss of PFP (log-rank test; P < .01). After adjustment, early loss of PFP was independently associated with a higher risk of mortality (adjusted hazard ratio, 1.21; 95% confidence interval, 1.01-1.45; P = .045). Regarding the impact of time to PTA on mortality, patients with intervention-free intervals of ≤3, 3 to 6, and 6 to 12 months had similar trends of lower survival. Early loss of PFP is an independent risk factor for mortality in chronic HD patients. A comprehensive strategy for maintaining PFP and reducing dysfunctional AVAs may be required.

Combined proximal tubulopathy, crystal-storing histiocytosis, and cast nephropathy in a patient with light chain multiple myeloma.

BACKGROUND: The diagnosis of myeloma, a plasma dyscrasia, often results from the workup of unexplained renal disease. Persistent renal failure in myeloma is commonly caused by tubular nephropathy due to circulating immunoglobulins and free light chains. Myeloma cast nephropathy is characterized by crystalline precipitates of monoclonal light chains within distal tubules. Immunoglobulin crystallization rarely occurs intracellularly, within proximal tubular cells (light chain proximal tubulopathy) and interstitial histiocytes (crystal-storing histiocytosis). We present a case report of a rare simultaneous occurrence of light chain proximal tubulopathy, crystal-storing histiocytosis, and myeloma cast nephropathy in a patient with κ light chain multiple myeloma. CASE PRESENTATION: A 48-years-old man presented with uremia and anemia. Laboratory examination revealed low levels of serum IgG, IgA, and IgM. Serum and urine immunofixation electrophoresis showed a free κ monoclonal band. Bone marrow aspiration and biopsy revealed hypercellularity with marked plasmacytosis. Light microscopy revealed eosinophilic cuboid- and rhomboid-shaped crystals in the cytoplasm of proximal tubular epithelial cells, diffuse large mononuclear and multinuclear cells in the interstitium, and obstructed distal tubules with cast and giant cell reaction. Immunohistochemical examination indicated intense staining for κ light chains within casts, histiocytes, and tubular epithelial cells. Electron microscopy revealed electro-dense cuboid-, rhomboid-, or needle-shaped crystalline inclusions in proximal tubular epithelial cells and interstitial histiocytes. According to these results, we confirmed that this patient with myeloma exhibited simultaneous light chain proximal tubulopathy, crystal-storing histiocytosis, and myeloma cast nephropathy, which were attributed to monoclonal κ light chains. In addition to dialysis, the patient received induction chemotherapy with a combination of bortezomib, cyclophosphamide, and dexamethasone, followed by maintenance therapy with thalidomide. However, the patient did not regain renal function even when less than 5% plasma cells were detected in the bone marrow. CONCLUSION: To the best of our knowledge, this is the first report of simultaneous light chain proximal tubulopathy, crystal-storing histiocytosis, and myeloma cast nephropathy in κ light chain multiple myeloma.

Simultaneous occurrence of fibrillary glomerulonephritis and renal lesions in nonmalignant monoclonal IgM gammopathy.

BACKGROUND: Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that seldom coexists with other diseases. Membranoproliferative glomerulonephritis is a pathologic finding of renal lesions associated with IgM-secreting monoclonal proliferations. We present a case study of a patient with unusual simultaneous FGN and IgM-related renal disorder in nonmalignant monoclonal IgM gammopathy. CASE PRESENTATION: A 63-year-old male presented with nephrotic syndrome and elevated serum creatinine levels. Laboratory examination revealed elevated levels of serum IgM and low C3 levels. Serum and urine immunofixation electrophoresis showed a monoclonal IgM with a kappa light chain. A bone marrow biopsy revealed less than 5 % bone marrow infiltration by lymphoplasmacytic lymphoma, and a renal biopsy revealed mesangiocapillary glomerulonephritis on light microscopy. Immunofluorescent and immunohistochemical staining indicated granular deposits of immunoglobulin G in the mesangium and granular deposits of immunoglobulin M and κ light chains along the capillary wall. Electron microscopy revealed randomly arranged nonbranching fibrils of approximately 15 nm in diameter in the glomerular mesangium and subendothelial electron-dense deposits. According to these results, we confirmed FGN and membranoproliferative glomerulonephritis, which were attributed to monoclonal IgM deposits. CONCLUSION: To the best of our knowledge, this is the first report of simultaneous FGN and membranoproliferative glomerulonephritis in nonmalignant IgM monoclonal gammopathy.