Nephrol Dial Transplant Research Articles

#2470 Isolated diastolic hypertension in hemodialysis patients

Abstract Background and Aims Isolated diastolic hypertension (IDH) is relatively rare in the general population (prevalence about 6.5%, Front Cardiovasc Med. 2021;8:810105) and of uncertain etiologic implications. The prevalence of this alteration in the hemodialysis (HD) population and the etiologic implications of IDH have not been studied. Method We investigated the prevalence and the risk for all-cause death and cardiovascular events of isolated diastolic hypertension in a population of 534 HD patients enrolled in 7 centres in 3 European countries (the EURECA-m working group). BP was measured by a golden standard method in this population (48 h ABPM) using well-validated instruments (AAMI/ESH/ISO). Along with recommendations by the European Society of Hypertension guidelines, recordings were made at 15-minute intervals during the day and 30 minutes at night. According to a consensus document by the EURECAm working group (Nephrol Dial Transplant. 2019;34:1542-1548), isolated diastolic hypertension was defined as 48 h diastolic BP > 80 mmHg with a systolic BP <130. Results Among 534 HD patients, thirty-one (5.8%) had isolated diastolic HTN, which is very close to the prevalence estimated in the general population (6.5%). During a mean follow-up of 2.6 years, 138 patients died, 188 had at least one CV event, and 249 experienced the combined event. In univariate analyses, diastolic hypertension was associated with death (HR 0.21; 95% CI: 0.05-0.86, P = 0.03) and the combined outcome of death and CV events (HR 0.42, 95% CI: 0.20-0.88, P = 0.02). However, these associations were no longer significant after adjustment for age and sex (all P > 0.45). Additional sensitivity analyses substantially confirmed these findings. No effect modification by age or gender was observed in these associations. Conclusion In a large cohort of HD patients studied by state-of-the-art 48-hour BP monitoring, the prevalence of isolated diastolic hypertension in HD patients (5.8%) is close to that registered in the general population (6.5%). This alteration predicts the risk for clinical outcomes in unadjusted analyses but not after adjustment for age and sex. Isolated diastolic hypertension is as rare as it is in the general population and unlikely to contribute to the high risk of adverse clinical outcomes in the dialysis population.

FRI091 Treatment Of Secondary Hyperlipidemia Due To Nephrotic Syndrome

Abstract Disclosure: J. Girard: None. H. Quadri: None. B. Jiang: None. B.K. Force: None. L. Abushamat: None. R.S. Aguirre: None. Introduction: Secondary Hyperlipidemia associated with nephrotic syndrome contributes to significant cardiovascular morbidity. The elevated atherogenic lipoprotein levels are caused by upregulation of HMG-CoA reductase and downregulation of lipoprotein lipase. More recently, studies in mice have linked PCSK9 and Inducible Degrader of the LDL Receptor (IDOL) as primary contributors to hypercholesterolemia in nephrotic syndrome due to the decrease in LDL receptor recycling (1). Treating nephrotic syndrome is the first-line treatment for the associated secondary hyperlipidemia. Since exposure time to atherogenic lipoproteins matters in the development of cardiovascular disease, statins, with or without ezetimibe, are utilized. PCSK9 inhibitors are initiated if LDL remains elevated despite these measures. This case report highlights a severe case of hypercholesterolemia associated with nephrotic syndrome and treatment response. Clinical Case: A 55-year-old male with no significant past medical history presented to the emergency department with shortness of breath and lower extremity edema. He denied a family and personal history of premature cardiovascular disease. Initial evaluation revealed a serum total cholesterol on 10x dilution of 833.9 (</=200mg/dL), calculated LDL 718mg/dL (<100mg/dL), triglycerides 381mg/dL (<150mg/dL), HDL 39.3mg/dL (40-60mg/dL), Apo B >400mg/dL (<90mg/dL), and Lp(a) 17.5mg/dL (<75mg/dL). His serum albumin was <1.5g/dL (4.2-4.5g/dL), creatinine 2mg/dL (0.7-1.3mg/dL), and 24-hour calculated urinary protein level 10,294mg/24-hour (30-150mg/24-hour). A kidney biopsy revealed a mixed Type III and Type V Lupus Nephritis. The patient started lupus treatment along with atorvastatin 80mg qHS, fenofibrate 45mg daily, and ezetimibe 10mg daily. His LDL decreased to 418mg/dL (<100mg/dL) after 15 days. The patient continued to have undetectable albumin although kidney function improved after 2 months. We planned to initiate PCSK9 inhibitor treatment for further LDL reduction pending treatment of lupus, but patient died from septic shock prior to initiation. Conclusion: This case illustrates that extremely elevated LDL levels from nephrotic syndrome resulted in a nearly 60% reduction of LDL with statin and ezetimibe treatment. Statins, ezetimibe and PCSK9 inhibitor therapy should be considered stepwise when treating secondary hyperlipidemia from nephrotic syndrome. 1. LIU S, VAZIRI ND. ROLE OF PCSK9 AND IDOL IN THE PATHOGENESIS OF ACQUIRED LDL RECEPTOR DEFICIENCY AND HYPERCHOLESTEROLEMIA IN NEPHROTIC SYNDROME. NEPHROL DIAL TRANSPLANT. 2014 MAR;29(3):538-43. DOI: 10.1093/NDT/GFT439. EPUB 2013 OCT 28. PMID: 24166456 Presentation: Friday, June 16, 2023

Choosing fluids to reduce the risk of delayed graft function after deceased donor kidney transplantation

Delayed graft function (DGF) after deceased donor kidney transplantation, defined clinically as the need for at least one dialysis session within the first week after transplantation, is a common occurrence. 1 Swanson KJ Bhattarai M Parajuli S Delayed graft function: current status and future directions. Curr Opin Organ Transplant. 2023; 28: 1-7 Crossref PubMed Scopus (0) Google Scholar Use of organs that are predisposed to DGF is increasing, 2 NHS Blood and TransplantOrgan and tissue donation and transplantation. Activity Report 2021/22. nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/27108/activity-report-2021-2022.pdfDate accessed: March 23, 2023 Google Scholar meaning it is important to consider the clinical sequelae of DGF. In a systematic review and meta-analysis of 38 studies, 3 Li MT Ramakrishnan A Yu M et al. Effects of delayed graft function on transplant outcomes: a meta-analysis. Transplant Direct. 2023; 9: e1433 Crossref PubMed Scopus (1) Google Scholar DGF was associated with adverse short-term and long-term outcomes, including risk for rejection, graft failure, and (in single-centre studies only) all-cause mortality. Some studies suggest the duration of DGF is more important than its occurrence. 4 Schrezenmeier E Müller M Friedersdorff F et al. Evaluation of severity of delayed graft function in kidney transplant recipients. Nephrol Dial Transplant. 2022; 37: 973-981 Crossref PubMed Scopus (2) Google Scholar However, any DGF has a real-world impact on patients and can influence decision making for clinicians. For example, a third of North American transplant professionals indicated in a survey that the risk of DGF had a role in their willingness to accept organs, 5 Jadlowiec CC Hippen B Gill J et al. Current opinions on DGF management practices: a survey of the United States and Canada. Clin Transplant. 2023; 37: e14949 Crossref PubMed Scopus (0) Google Scholar and strategies to reduce DGF are a clinical priority. A simple intervention to reduce DGF might relate to optimising intravenous fluid replacement. Isotonic sodium chloride (0·9% saline) is the standard of care in many transplantation units. However, 0·9% saline might be harmful due to its high chloride content, which causes metabolic acidosis and can promote acute kidney injury, thus DGF. 6 Yunos NM Bellomo R Hegarty C Story D Ho L Bailey M Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012; 308: 1566-1572 Crossref PubMed Scopus (844) Google Scholar Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trialAmong patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. Full-Text PDF

Six pills less: no benefit for bicarbonate supplementation in renal allograft recipients

Metabolic acidosis (defined as serum bicarbonate <22 mmol/L) is frequent in patients with chronic kidney disease and is associated with disease progression. 1 Chapter 3: management of progression and complications of CKD. Kidney Int Suppl (2011). 2013; 3 (No authors listed): 73-90 Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar Several prospective trials and meta-analyses 2 Hultin S Hood C Campbell KL Toussaint ND Johnson DW Badve SV A systematic review and meta-analysis on effects of bicarbonate therapy on kidney outcomes. Kidney Int Rep. 2020; 6: 695-705 Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar , 3 Witham MD Band M Chong H et al. Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT. Health Technol Assess. 2020; 24: 1-90 Crossref PubMed Scopus (8) Google Scholar , 4 Di Iorio BR Bellasi A Raphael KL et al. Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI study. J Nephrol. 2019; 32: 989-1001 Crossref PubMed Scopus (70) Google Scholar , 5 Dubey AK Sahoo J Vairappan B Haridasan S Parameswaran S Priyamvada PS Correction of metabolic acidosis improves muscle mass and renal function in chronic kidney disease stages 3 and 4: a randomized controlled trial. Nephrol Dial Transplant. 2020; 35: 121-129 PubMed Google Scholar , 6 Navaneethan SD Shao J Buysse J Bushinsky DA Effects of treatment of metabolic acidosis in CKD: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2019; 14: 1011-1020 Crossref PubMed Scopus (60) Google Scholar have suggested potential positive effects (of low certainty) of sodium bicarbonate treatment on chronic kidney disease progression, and bicarbonate supplementation is recommended in patients with chronic kidney disease with serum bicarbonate less than 22 mmol/L. 1 Chapter 3: management of progression and complications of CKD. Kidney Int Suppl (2011). 2013; 3 (No authors listed): 73-90 Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar However, protective mechanisms are not fully understood and it is difficult to determine whether acidosis is a cause or consequence of renal function decline. Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trialIn adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. Full-Text PDF

DISC-0974, an Anti-Hemojuvelin (HJV) Monoclonal Antibody, Reduced Hepcidin and Improved Anemia in a Rat Model of Chronic Kidney Disease

Introduction DISC-0974 is a humanized monoclonal antibody against hemojuvelin (HJV) and is currently in Phase I clinical studies. HJV is a pathway-specific coreceptor for bone morphogenetic protein (BMP) signaling that regulates hepcidin expression and iron metabolism. Loss of function mutations of the HFE2 gene encoding HJV in humans cause profound reductions in hepcidin synthesis and severe iron overload. Consequently, it is hypothesized that pharmacological reduction of HJV activity will lead to reduction of hepcidin synthesis and increased iron availability. This hypothesis has been confirmed in studies of DISC-0974 in rodents and non-human primates and in healthy human volunteers. We have conducted studies to evaluate the effect of DISC-0974 in an animal model of CKD anemia. Anemia is a common complication in patients with CKD and has been associated with multiple adverse outcomes in this population. In CKD hepcidin is increased because of both reduced renal clearance and increased synthesis. This increase is believed to be a central contributor to the development of anemia by reducing the availability of iron from systemic iron stores and by reducing dietary iron absorption. Supporting this hypothesis, treatment with hepcidin lowering drugs has been demonstrated to increase serum iron and to increase hemoglobin (Sheetz et al, Br J Clin Pharmacol. 2019;85:935-948). We hypothesize that by downregulating hepcidin, DISC-0974 will have beneficial effects in treating anemia in the CKD patients because it will make iron available for improved erythropoiesis and increased hemoglobin synthesis as well as reducing erythropoietin resistance. Material and Methods The effect of DISC-0974 on improving anemia was evaluated in an adenine-induced rat model of CKD. In this study, renal impairment was induced by giving Sprague Dawley rats a diet containing 0.75% adenine for 3 weeks to induce kidney injury and then switched to a control diet for the remainder of the study (i.e., 3 more weeks). DISC-0974 (20 mg/kg) or vehicle (n-5/group) was administered intravenously once per week starting on Day 7 and continuing to Day 35. An additional group of rats (n=5/group) was fed with the control diet for the entire study and dosed intravenously with vehicle. Rats were euthanized on Day 42. Blood was collected on Days 0, 7, 21, 35, and 42 for evaluation of hematology parameters, as well as serum iron and hepcidin. Livers were also collected at study end for evaluation of hepcidin gene (HAMP) mRNA expression level. Results Consistent with a previous report (Sun et al, Nephrol Dial Transplant. 2013;28:1733-1743), the 0.75% adenine diet induced kidney dysfunction, as evidenced by marked increase in both serum creatinine and blood urea nitrogen. Rats on adenine diet developed reduced serum iron, reduced red cell production, and lowered hemoglobin with a hypochromic microcytic profile reflecting reduced iron availability. CKD rats appeared to tolerate DISC-0974 treatment well, as DISC-0974 @ 20mg/kg did not affect body weight. Consistent with the mechanism of action of blocking the formation of the BMP/BMPR/HJV complex, DISC-0974 reduced HAMP gene expression in the liver as measured at the end the study, which led to reduced serum hepcidin and increased serum iron concentration. Cellular hemoglobinization measured as reticulocyte Hemoglobin was increased. The maximum improvement in hemoglobin by DISC-0974 compared to the vehicle group was 17g/L in the rat CKD model. Conclusions We conclude that treatment with DISC-0974 at a dose that reduces hepcidin gene expression is able to increase iron availability and substantially prevents the reduction in hemoglobin that is seen in animals that develop adenine-induced renal impairment. This study supports the development of DISC-0974 for the treatment of patients with CKD anemia. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Risk Prediction Score for Renal Replacement Therapy in Critically Ill Septic – Acute Kidney Injury Patients

Introduction: Acute kidney injury (AKI) is a major complication in critically ill septic patients and is associated with increased morbidity and mortality. A recent study suggested a risk score based on patient’s chronic comorbidities and acute events at intensive care unit (ICU) admission as a reliable tool for predicting AKI in critically ill adult population. The aim of this study was to adapt this score to septic-AKI patients and evaluate its prognostic value as predictor of the need for renal replacement therapy (RRT) at ICU admission. Methods: This is a retrospective analysis of 399 septic-AKI patients admitted to the Division of Intensive Medicine of the Centro Hospitalar Universitário Lisboa Norte between January 2008 and December 2014. The Kidney Disease Improving Global Outcomes (KDIGO) classification was used to define AKI. The Renal Replacement Therapy Risk Score was adapted from the AKI risk prediction score proposed by Malhotra et al (Nephrol Dial Transplant. 2017;32:814-22). Results: Fifty two percent of patients were KDIGO stage 3, 25.8% KDIGO stage 2 and 22.3% KDIGO stage 1. Twenty seven percent of patients required RRT. Patients requiring RRT had higher risk score than those who did not (6.6±2.5 vs 5.1 ±2.6, p&lt;0.001). An optimal cut-off value of ≥ 6 in this score predicted the need for RRT with sensitivity 0.630 and specificity 0.391. Conclusion: The RRT risk score at ICU admission was independently associated with the requirement of RRT septic-AKI patients. The assessment of this ratio is simple and can prove useful in identifying patients at risk for need of RRT.

MO705: Factors Associated with Uncontrolled Ambulatory Hypertension in Peritoneal Dialysis Patients

Abstract BACKGROUND AND AIMS Hypertension among patients on long-term peritoneal dialysis (PD) is common and remains often inadequately control (Cocchi et al. Prevalence of hypertension in patients on peritoneal dialysis: results of an Italian multicentre study. Nephrol Dial Transplant. 1999; 14(6): 1536–40; Vaios et al.. Assessment and management of hypertension among patients on peritoneal dialysis. Clin J Am Soc Nephrol. 2019; 14(2): 297–305). The aim of the present study was to describe the epidemiology of hypertension using the ‘gold-standard’ method of ambulatory blood pressure monitoring (ABPM) and to identify determinants of inadequate ambulatory blood pressure (BP) control in this high-risk population. METHOD In 140 stable patients receiving PD in four centers of Northern Greece, we performed 24-h ABPM using the oscillometric Mobil-O-Graph device (IEM, Stolberg Germany) (Franssen and Imholz. Evaluation of the Mobil-O-Graph new generation ABPM device using the ESH criteria. Blood Press Monit. 2010; 15(4): 229–31). Hypertension was defined as 24-h ambulatory BP ≥ 130/80 mmHg or current use of at least 1 BP-lowering medication (Williams et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018; 36(10): 1953–2041). The volume status of study participants was assessed with the method of bioimpedance spectroscopy (Fresenius Medical Care, Bad Homburg, Germany). Univariate and multivariate binary logistic regression analysis was performed to identify factors that were independently associated with uncontrolled ambulatory hypertension. RESULTS Ambulatory hypertension was diagnosed in 95% of the patients enrolled in the study. Despite the fact that 96.9% of hypertensives were being treated with an average of 2.4 BP-lowering medications daily, adequate control of 24-h ambulatory BP was achieved in only 38.3% of them. In univariate regression analysis, there was a significant interaction of uncontrolled ambulatory hypertension with the mode of PD, history of cardiovascular disease and smoking status. In multivariate analysis, among variables inserted in the model, the higher overhydration index in bioimpedance spectroscopy [odds ratio (OR): 1.308; 95% confidence interval (CI): 1.023–1.673/L higher overhydration] and the history of cardiovascular disease (OR: 3.069; 95% CI: 1.157–8.140) were the two factors that were associated with higher odds of uncontrolled ambulatory hypertension. In contrast, the presence of residual diuresis ≥ 0.5 L/24 h (OR: 0.304; 95% CI: 0.105–0.881) was the only parameter associated with lower odds of inadequate ambulatory BP control. CONCLUSION Among patients on PD, ambulatory hypertension is highly prevalent and remains often poorly controlled, despite the extensive use of antihypertensive drug therapy. Achievement of adequate volume control and long-term preservation of residual kidney function appear to be two attractive non-pharmacological strategies for optimization of the management of hypertension in this high-risk population.

Mortality in solid organ transplant recipients with COVID-19: More than meets the eye

Mortality in solid organ transplant recipients with COVID-19: More than meets the eye

Facilitators and barriers to living donor kidney transplantation

Facilitators and barriers to living donor kidney transplantation

A CASE OF FANCONI SYNDROME SECONDARY TO LEGIONELLA PNEUMONIA

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Fanconi syndrome is a generalized dysfunction of the renal proximal tubules without primary glomerular involvement, characterized by wasting of phosphate, amino acids, or glucose by the proximal tubules. In addition, hypokalemia, hypouricemia, metabolic acidosis and proteinuria can be found (1, 2, 3). Acquired forms of Fanconi syndrome are caused by paraproteinemia, Sjogren syndrome, Primary Biliary Cirrhosis, and medications like cisplatin. Infectious diseases have not been reported as a common cause of Fanconi Syndrome (2). In this case report, we present an extremely rare case of Legionella pneumonia complicated by Fanconi syndrome. CASE PRESENTATION: A 42 year old woman with no past medical history was admitted to the hospital with fever, myalgias, diarrhea, and dyspnea. Vital signs on admission were; temperature 38.4 °C, blood pressure 114/57 mmHg, pulse 102 beats/min, respiration rate 20. Labs showed a white blood cell count of 10.9 x 10^3/ul, sedimentation rate of 126 mm/hr, procalcitonin 0.17 ng/ml, and C-reactive protein of 22.9 mg/dL. A CXR revealed a mild left lower lobe opacity compatible with pneumonia (figure 1). The patient tested positive for the Legionella urine antigen and was diagnosed with Legionella pneumonia. Multiple electrolyte abnormalities coexisted with the pneumonia including hypokalemia of 2.8mm/l, hypouricemia of 1.9mg/dl, hypophosphatemia of 1.8mg/dl and hypocalcemia of 8mg/dl. The patient's renal function was normal with no indication of metabolic acidosis. The urinalysis showed 4+ proteinuria, glucosuria and bilirubin with no WBCs. The patient was diagnosed with Fanconi Syndrome based on these findings. The patient was treated for Legionella pneumonia with Levaquin and improved clinically and serum electrolytes normalized. The repeat urinalysis after treatment revealed trace amounts of protein, negative glucose, decreased urobilinogen, and negative bilirubin. DISCUSSION: In this case because the electrolyte abnormalities disappeared after treatment for Legionella pneumonia and there was no evidence of other causes of Fanconi syndrome, it is most likely that Fanconi syndrome was associated with Legionella pneumonia. However, we are uncertain; (1) if Legionella pneumophila entered from basolateral/apical side of the renal proximal tubular cells and (2) why it specifically targeted the proximal tubular cells, developing reabsorption defects but not distal tubular cells. To our knowledge, only two cases (2, 3) have been reported in the literature linking Fanconi syndrome to Legionella pneumonia which makes our case exceedingly rare. CONCLUSIONS: This is an extremely rare case of Fanconi syndrome associated with Legionella pneumonia. Further studies are needed to understand the mechanisms responsible for electrolyte imbalances, which is important for the management of this potentially fatal infection. REFERENCE #1: Klootwijk ED, Reichold M, Unwin RJ, Kleta R, Warth R, Bockenhauer D. Renal Fanconi syndrome: taking a proximal look at the nephron. Nephrol Dial Transplant 30: 1456-1460, 2015. REFERENCE #2: Kinoshita-Katahashi, N., Fukasawa, H., Ishigaki, S., Isobe, S., Imokawa, S., Fujigaki, Y., & Furuya, R. (2013). Acquired Fanconi syndrome in patients with Legionella pneumonia. BMC nephrology, 14, 171. REFERENCE #3: Ryuge, A., Ito, Y., Yamakawa, T., Tanaka, H., Yasui, H., Mashimo, S., Watanabe, K., Nomura, R., Suganuma, N., & Maruyama, S. (2016). Fanconi Syndrome Associated with Hyponatremia in Two Patients with Legionella Pneumonia. Internal medicine (Tokyo, Japan), 55(23), 3479–3484. DISCLOSURES: No relevant relationships by Dilesha Kumanayaka, source=Web Response No relevant relationships by Richard Miller, source=Web Response No relevant relationships by Rutwik Patel, source=Web Response No relevant relationships by Bhavik Patel, source=Web Response

Cardiovascular Harm From Egg Yolk and Meat: More Than Just Cholesterol and Saturated Fat.

Cardiovascular Harm From Egg Yolk and Meat: More Than Just Cholesterol and Saturated Fat.

Improving the "second generation Daugirdas equation" to estimate Kt/V on the once-weekly haemodialysis schedule.

The haemodialysis (HD) dose, as expressed by Kt/V urea, is currently routinelyestimated with the second generation Daugirdas (D2) equation (Daugirdas in J Am Soc Nephrol 4:1205-1213, 1993). This equation, initially devised for a thrice-weekly schedule, was modified to be used for all dialysisschedules (Daugirdas et al. in Nephrol Dial Transplant 28:2156-2160, 2013), by adopting a variable factor that adjusts for the urea generation (GFAC) over the preceding inter-dialysis interval (PIDI, days). This factorwas set at 0.008 for the mid-week session of the standard thrice-weekly HD schedule. In theory, by setting PIDI = 7, one could get GFAC = 0.0025, to be used in patients on the once-weekly (1HD/wk) schedule, but actually this has never been tested. Moreover, GFAC was derived not taking into account the residual kidney urea clearance (Kru). Aim of the present study was to provide a specific value of GFAC for patients on aonce-weeklyhemodialysis schedule. The equation to predict GFAC (GFAC-1) in the 1HD/wk schedule was established in a group of 80 historical Italian patients (group 1) and validated in a group of 100 historical Spanish patients (group 2), by comparing the Kt/V computed using GFAC-1 (Kt/VGFAC-1) with the reference Kt/V (Kt/VSS) values, as computed with the web-based Solute-Solver software (SS) (Daugirdas et al. in Am J Kidney Dis 54:798-809, 2009). Three more sets of Kt/V (Kt/V0.008, Kt/V0.0025 and Kt/V0.0035) values were computed using the GFAC of the original D2 equation (0.008), the GFAC predicted by PIDI/7 (0.0025) and the mean observed GFAC-1 (0.0035), respectively. They were compared with the reference Kt/VSS values. The predicting equation obtained from group 1 was: GFAC-1 = 0.0022 + 0.0105 × Kru/V (R2 = 0.93). Mean Kt/VSS in the group 2 was 1.54 ± 0.29 SD (N = 500 HD sessions). The mean percent differences for Kt/V0.008, Kt/V0.0025, Kt/VGFAC-1, and Kt/V0.0035 were 5.1 ± 1.0%, -1.4 ± 0.7%, 0.0 ± 0.3%, -0.3 ± 0.7%, respectively. No statistically significant difference was found between Kt/V values, except for Kt/V0.008. A linear relationship was found between GFAC and Kru/V in patients on the 1HD/wk schedule. Such a relationship is able to improve the "second generation Daugirdas equation" for an accurate estimate of the single pool Kt/V in this setting. However, a simple replacement in the D2 equation of 0.008 with the mean observed GFAC (0.0035) could suffice in the clinical practice.

COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients.

The COVID‐19 pandemic has brought unprecedented challenges to the transplant community. The reduction in transplantation volume during this time is partly due to concerns over potentially increased susceptibility and worsened outcomes of COVID‐19 in immunosuppressed recipients. The consequences of COVID‐19 on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID‐19 between March 13 and May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, P = .03) and were at a higher risk of mortality (34% vs. 16%, P = .02). Intubation was required in one third of hospitalized patients in each group, and portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID‐19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk. Understanding the impact of COVID‐19 on waitlist patients in comparison to transplant recipients may aid centers in weighing the risks and benefits of transplantation in the setting of ongoing COVID‐19.

Acute Coronary Syndrome in Patients with Thrombotic Thrombocytopenic Purpura

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening clinical syndrome characterized by microangiopathy and a variable degree of end-organ ischemic damage. Cardiac involvement has been recognized as a major cause of mortality in these patients (Patschan et al, Nephrol Dial Transplant, 2006; Benhamou et al, J Thromb. Haemost, 2015). In this study, we aim to investigate clinical predictors and outcomes of acute coronary syndrome in the setting of TTP admissions. Methods: The National Inpatient Sample (NIS) was queried for all hospitalizations with a primary diagnosis of thrombotic microangiopathy (ICD- 9-CM code 4466 and ICD-10-CM code M3.11) from 2002 to 2017. Using ICD-9-CM procedure codes (9972), (9971), and (9979), as well as ICD-10-CM procedure codes (6A551Z3) and (6A550Z3) we identified patients who received plasma exchange (PLEX) during the same admission. Due to the wide spectrum of thrombotic microangiopathy diseases, we decided to include only those who received PLEX to get a more specific subpopulation who were presumed to have TTP. We stratified patients based on whether or not they had acute coronary syndrome (ACS) during the admission, defined as presence of any ICD code for either ST-segment elevation myocardial infarction (STEMI), Non-STEMI, or unstable angina. Baseline characteristics and inpatient outcomes were compared between groups. Statistical analysis was performed using SPSS v26 (IBM Corp, Armonk, NY, USA). The odds ratio (OR) and 95% confidence interval (CI) were calculated using the Cochran-Mantel-Haenszel test. A multivariate regression model was deployed to assess predictors of inpatient mortality. Complex weights were used throughout all calculations, enabling appropriate national projections. Results: A total of 15,640 patients with the diagnosis of thrombotic microangiopathy were identified during the studied period. Of those, 6,214 patients had received PLEX treatment during their admission (39.7%). The annual admission rate for TTP was ranging between 5-7/100,000 admissions. Patients had a mean age of 47.8 years; 67% were females, and 46.5% were Caucasian. Stratifying by geographic region, 24% were from the Northeast, 21% from the Midwest, 42% from the South, and 13% from the West. The most common primary payer was private insurance (42.7%). Overall inpatient mortality was 9.1%. The most common complications reported included acute kidney injury (42.5%), followed by acute respiratory failure (14.9%), incident dialysis (14.3%), acute encephalopathy (7.7%), acute heart failure (7.3%), acute cerebrovascular accident (7.2%), and acute coronary syndrome (6.3%). ACS was documented in 6.7% of patients. Compared with patients without ACS, those with ACS were relatively older and had a relatively higher prevalence of coronary artery disease, dyslipidemia, diabetes mellitus, essential hypertension, chronic kidney disease, and heart failure. Patients with ACS had a 3-fold higher in-hospital mortality and a longer mean hospital stay (19 days vs. 15 days, P&amp;lt;0.001). Using stepwise logistic regression, we identified age (aOR 1.03; 95% CI, 1.02 - 1.03; P &amp;lt;0.001), history of heart failure (aOR 2.02; 95% CI, 1.53-2.67; P &amp;lt;0.001), and history of coronary artery disease (aOR 2.69; 95% CI, 2.03 - 3.57; P &amp;lt;0.001) as independent predictors of ACS among patients hospitalized with TTP. On another regression analysis, certain complications were more prevalent in the ACS group including acute cerebrovascular accidents, acute heart failure, acute kidney injury, cardiogenic shock, and respiratory failure. Conclusion: Despite wider utilization of therapeutic plasmapheresis and improved supportive treatments for patients with TTP, associated morbidity and mortality remain significant. We demonstrate from this large retrospective cohort that ACS is an independent predictor of higher morbidity and mortality in TTP patients. We identified older age, history of heart failure, and history of coronary artery disease as independent predictors of ACS among patients admitted with TTP. Further studies are warranted to develop risk stratification models for patients with TTP. Figure Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

A DEEP-TISSUE MASSAGE WITH UNINTENDED CONSEQUENCES

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Rhabdomyolysis is a common clinical syndrome that can result from a variety of insults that are generally evident, and well-described. We report a patient with rhabdomyolysis associated with an unusual inciting event. CASE PRESENTATION: A 44-year-old gentleman presented to the hospital with upper extremity myalgias. About 48 hours prior to presentation, he received an upper body massage at a commercial spa over a 30-60 minute duration. Hours after, he sustained a fall from standing via a relatively low mechanism of injury. After waking from sleep the following day his symptoms worsened and he developed dark-brown urine discoloration, prompting his presentation to the hospital. He denied any new medications, excessive physical exertion, or prior similar episodes in himself or relatives. His medication list included gabapentin, oxycodone, and doxepin, without concurrent anabolic steroid use, or illicit drug use. On examination, he was mildly tachycardic but otherwise hemodynamically normal. He had a general muscular build, and bilateral deltoid, upper arm, and forearm edema and tenderness. There was no evidence of neurovascular compromise. Workup showed an elevated creatine phosphokinase (CPK) (66,100 U/L), myoglobinuria (3+ blood, 0-5 RBCs), with unremarkable potassium, phosphate, urine drug screen, and plain films of the affected extremities. The patient was admitted to the medical ICU for hydration and neurovascular monitoring. His serial CPK levels gradually improved over days (1,483 U/L) and he was discharged home. DISCUSSION: Rhabdomyolysis occurs when injured myocytes release their intracellular contents into the extracellular space, which results in subsequent myoglobinuria. Supporting diagnostic features include elevated serum muscle enzymes (CPK =500-1000 U/L), myoglobinuria, proteinuria, hyperkalemia, hyperphosphatemia, and acute kidney injury. Insults include physical, ischemic, chemical and biologic causes. Physical insults such as prolonged exertion and immobilization are established causes for rhabdomyolysis. However, only one previously published report has implicated massage therapy, in which an elderly man developed rhabdomyolysis after a 120-minute massage by two therapists. While massage remains a common Complementary and Alternative Medicine modality, serious adverse events rarely may occur. CONCLUSIONS: Our patient's course highlights a rare encounter which associates deep-tissue massage and rhabdomyolysis by close temporal association, anatomic distribution, and lack of other significant contributing causes. Reference #1: Zimmerman JL, Shen MC. Rhabdomyolysis. Chest. 2013 Sep;144(3):1058-1065. doi: 10.1378/chest.12-2016. Review. PubMed PMID: 24008958. Reference #2: Lai MY, Yang SP, Chao Y, Lee PC, Lee SD. Fever with acute renal failure due to body massage-induced rhabdomyolysis. Nephrol Dial Transplant. 2006 Jan;21(1):233-4. Epub 2005 Oct 4. PubMed PMID: 16204282. Reference #3: Yin P, Gao N, Wu J, Litscher G, Xu S. Adverse events of massage therapy in pain-related conditions: a systematic review. Evid Based Complement Alternat Med. 2014;2014:480956. doi: 10.1155/2014/480956. Epub 2014 Aug 12. Review. PubMed PMID: 25197310; PubMed Central PMCID: PMC4145795. DISCLOSURES: No relevant relationships by Jason Stankiewicz, source=Web Response No relevant relationships by Nevins Todd, source=Web Response

Ex vivo delivery of Mirococept: A dose-finding study in pig kidney after showing a low dose is insufficient to reduce delayed graft function in human kidney.

The complement system plays a pivotal role in the pathogenesis of ischemia-reperfusion injury in solid organ transplantation. Mirococept is a potent membrane-localizing complement inhibitor that can be administered ex vivo to the donor kidney prior to transplantation. To evaluate the efficacy of Mirococept in reducing delayed graft function (DGF) in deceased donor renal transplantation, we undertook the efficacy of mirococept (APT070) for preventing ischaemia-reperfusion injury in the kidney allograft (EMPIRIKAL) trial (ISRCTN49958194). A dose range of 5-25mg would be tested, starting with 10mg in cohort 1. No significant difference between Mirococept at 10mg and control was detected; hence the study was stopped to enable a further dose saturation study in a porcine kidney model. The optimal dose of Mirococept in pig kidney was 80mg. This dose did not induce any additional histological damage compared to controls or after a subsequent 3hours of normothermic machine perfusion. The amount of unbound Mirococept postperfusion was found to be within the systemic dose range considered safe in the Phase I trial. The ex vivo administration of Mirococept is a safe and feasible approach to treat DGF in deceased donor kidney transplantation. The porcine kidney study identified an optimal dose of 80mg (equivalent to 120mg in human kidney) that provides a basis for further clinical development.

EVEROLIMUS-INDUCED PULMONARY ALVEOLAR PROTEINOSIS

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare respiratory disease characterized by an excessive accumulation of lipoproteinaceous surfactant material in the distal air spaces. This is mostly the result of inadequate clearance of surfactant by alveolar macrophages. Autoimmune etiologies make up ∼90% of adult cases, however there are congenital and secondary etiologies as well (1). We present a unique case of drug induced PAP caused by everolimus use. CASE PRESENTATION: A 44 year old female, history of renal cell carcinoma (RCC) with lung metastasis, presents with 1 week of worsening shortness of breath following a round of chemotherapy and immunotherapy (nivolumab, ipilimumab, everolimus). Associated fever, vomiting and productive cough were also reported. On the scene, EMS reported an oxygen saturation of 81% on room air. In the ED, the patient was placed on BiPAP and started on scheduled breathing treatments, IV fluids and broad spectrum antibiotics. Chest exam revealed diffuse rales. Initial labs showed lactic acidosis without an elevated WBC. ABG showed PaO2 of 103 mmHg on 60% BiPAP. CT chest showed new onset loculated right-sided pleural effusion and extensive left-sided ground glassing, concerning for a crazy pavement appearance. Right-sided thoracentesis was attempted and failed as the fluid could not be aspirated. On Day 2, she was intubated due to worsening respiratory status. Bronchoalveolar lavage (BAL) sample was obtained. BAL cytology was negative for malignant cells or active inflammation, but showed an abundance of amorphous, eosinophilic, periodic acid-Schiff (PAS)-positive material. Bacterial, fungal and viral cultures and respiratory viral PCR were negative. She continued to decline and on day 8, in light of her terminal illness, her family decided to transition to hospice care. Compassionate extubation was done on day 9 and the patient expired shortly after. DISCUSSION: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor, often used in breast, pancreatic and renal carcinoma. Though there have been reports of PAP complicating sirolimus use, no such reports exist for everolimus (2). PAS stains of BAL or lung biopsy samples confirm the diagnosis of PAP. But without a sample, high index of clinical suspicion is needed to differentiate PAP from other pulmonary processes and intervene early. If diagnosed early, stopping the offending agent may be all that is needed. In those with moderate to severe symptoms, whole lung lavage (WLL) is the most accepted intervention. 30-50% of cases only require one lavage, others will require repeat at 6-12-month intervals. Cases refractory to WLL may require trials of GM-CSF inhaled therapy and rituximab but their efficacy has only been shown in autoimmune PAP (3). CONCLUSIONS: We present a case of everolimus induced pulmonary alveolar proteinosis in a patient with metastatic RCC. Diagnosis was confirmed with a PAS-positive BAL sample. Reference #1: Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003; 349:2527. Reference #2: Kadikoy H, Paolini M, Achkar K, et al. Pulmonary alveolar proteinosis in a kidney transplant: a rare complication of sirolimus. Nephrol Dial Transplant 2010; 25: 2795–2798 Reference #3: Kumar A, Abdelmalak B, Inoue Y, Culver DA. Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach. Lancet Respir Med 2018; 6:554. DISCLOSURES: No relevant relationships by Gnananandh Jayaraman, source=Web Response No relevant relationships by Ramesh Babu Kesavan, source=Web Response No relevant relationships by Robert Liu, source=Web Response No relevant relationships by Sivatej Sarva, source=Web Response

P0112BOWMAN'S CAPSULE RUPTURE ON RENAL BIOPSY IMPROVES THE OUTCOME PREDICTION OF ANCA-ASSOCIATED GLOMERULONEPHRITIS CLASSIFICATION

Abstract Background and Aims ANCA-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis (GN) and can lead to ESRD or death, even after aggressive immunosuppressive therapies (Jones et al, N Engl J Med, 363(2010), 211-220). The histological assessment of renal tissue can help in predicting the outcome and a 4-tiered classification based on glomerular lesions has been proposed to stratify these cases (Berden et al, J Am Soc Nephrol, 21(2010), 1628-1636). Subsequent studies, however, failed to confirm its predictive value (Tanna et al, Nephrol Dial Transplant, 30(2015), 1185-1192), stressing the need of new prognostic markers of the disease. The present study investigates whether additional histological features can improve the performance of the current classification in predicting the outcome of these patients. Method A retrospective series of biopsy-proven paucimmune crescentic GN has been collected between January 2012 and June 2018 from two Italian centers (San Gerardo Hospital, Monza and Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma). After the exclusion of patients with negative/unavailable serum ANCA testing, lacking clinical data, less than 12 months of follow-up, less than 5 glomeruli per biopsy and coexisting glomerular diseases, a final cohort of 52 cases was selected. Demographic and clinical data at the time of the diagnosis are reported in Figure, panel A. Renal biopsies have been reviewed by two experts in renal pathology and scored for multiple glomerular, tubulointerstitial and vascular lesions, as well as classified following the 4-tiered schema. The outcome of interest was time to need for RRT or death, whatever occurred first. Cox proportional hazards regression models were constructed with time to composite event, loss to follow-up or censoring (06/30/2019). Time at risk started at the date of renal biopsy. Histologic predictors were collapsed into binary variables (0-1 = low; 2-3 = high) and tested in univariate models, with the association expressed as hazard ratios (HRs) and 95% confidence intervals (CI); those showing a significant association with the outcome ( Figure, panel B) were included in a multivariable model together with a variable representing the Berden class. The prognostic performance of models including only the Berden class or the Berden class plus additional predictors was assessed using Harrell’s c-statistic. Results During a follow-up of 1,828 person-months, 13 composite events developed (8 deaths, 5 RRT), corresponding to an incidence rate of 7.1 (95% CI 4.2, 12.2) per 1,000 person-months. Of the tested predictors, Bowman’s capsule rupture (BCR, Figure, panel C) was significantly associated with the outcome (p = 0.023). Compared with a model including only Berden class (c = 0.67), the addition of this parameter significantly improved the prognostic performance (c = 0.76). In the multivariable model including Berden class, BCR remained significantly associated with the outcome (HR 3.61, 95% CI 1.15, 11.34; p = 0.028). Conclusion The present study demonstrated an improved performance of Berden classification in predicting patients’ outcome after the implementation of BCR. This can allow a better stratification of these cases, leading to tailored therapeutic approaches. Further investigations on a larger prospective cohort are required to confirm these results.

COVID-19 and the impact on kidney disease

Journal of Kidney CareVol. 5, No. 3 Keeping up with Kidney CareCOVID-19 and the impact on kidney diseasePeter EllisPeter EllisEmail: E-mail Address: [email protected]Registered Manager, Whitepost Healthcare and Independent Nursing and Educational Consultant, KentSearch for more papers by this authorPeter EllisPublished Online:2 Jun 2020https://doi.org/10.12968/jokc.2020.5.3.146AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Basile C, Combe C, Pizzarelli F et al. on behalf of the EUDIAL Working Group of ERA-EDTA. Recommendations for the prevention, mitigation and containment of the emerging SARS-CoV-2 (COVID-19) pandemic in haemodialysis centres. Nephrol Dial Transplant. 2020; 35(5):737–741. https://doi.org/10.1093/ndt/gfaa069 Google ScholarBowes C, Cairns H, Sharpe C. King's College Hospital NHS Foundation Trust acute peritoneal dialysis on intensive care units protocol. 2020. https://renal.org/wp-content/uploads/2020/04/KCH-Renal-Covid-Acute-PD-on-ICU-protocol-final.pdf (accessed 4 May 2020) Google ScholarCheng Y, Luo R, Wang K et al.. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020. 97(5):829–838. https://doi.org/10.1016/j.kint.2020.03.005 Google ScholarIkizler TA, Kliger AS. Minimizing the risk of COVID-19 among patients on dialysis. Nat Rev Nephrol. 2020 [epub ahead of print]. https://doi.org/10.1038/s41581-020-0280-y Google ScholarReynolds HR, Adhikari S, Pulgarin C et al.. Renin–angiotensin–aldosterone system inhibitors and risk of Covid-19. N Engl J Med. 2020 [epub ahead of print]. https://doi.org/10.1056/NEJMoa2008975 Google ScholarZhu L, Zhi-Gang S, Cheng X et al.. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metabolism. 2020 [epub ahead of print]. https://doi.org/10.1016/j.cmet.2020.04.021 Google Scholar FiguresReferencesRelatedDetails 2 May 2020Volume 5Issue 3ISSN (print): 2397-9534ISSN (online): 2397-9542 Metrics History Published online 2 June 2020 Published in print 2 May 2020 Information© MA Healthcare LimitedKeywordsCOVID-19kidney diseasemortality rateskeywordPDF download

Glomerular Filtration Rate Calculation Based on Serum Creatinin and Cystatin C in Type 2 Diabetic Patients

Glomerular Filtration Rate Calculation Based on Serum Creatinin and Cystatin C in Type 2 Diabetic Patients