Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy.

BACKGROUND: Circulating serum autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are a key biomarker in the diagnosis and monitoring of primary membranous nephropathy (MN). However, little is known about the appearance and trajectory of PLA2R-AB before the clinical diagnosis of MN. METHODS: Using the Department of Defense Serum Repository, we analyzed PLA2R-AB in multiple, 1054 longitudinal serum samples collected before diagnosis of MN from 134 individuals with primary MN, 35 individuals with secondary MN, and 134 healthy volunteers. We evaluated the presence and timing of non-nephrotic range proteinuria (NNRP) and serum albumin measurements in relation to PLA2R-AB status. RESULTS: Analysis of PLA2R-AB in longitudinal serum samples revealed seropositivity in 44% (59 out of 134) of primary MN cases, 3% (one out of 35) of secondary MN cases, and in 0% of healthy controls. Among patients with MN, PLA2R-AB were detectable at a median of 274 days before renal biopsy diagnosis (interquartile range, 71-821 days). Approximately one third of the participants became seropositive within 3 months of MN diagnosis. Of the 21 individuals with documented prediagnostic NNRP, 43% (nine out of 21) were seropositive before NNRP was first documented and 28.5% (six out of 21) were seropositive at the same time as NNRP; 66% (39 out of 59) of those seropositive for PLA2R-AB had hypoalbuminemia present at the time antibody was initially detected. Twelve participants (20%) were seropositive before hypoalbuminemia became apparent, and eight participants (14%) were seropositive after hypoalbuminemia became apparent. CONCLUSIONS: Circulating PLA2R-AB are detectable months to years before documented NNRP and biopsy-proven diagnosis in patients with MN.

Inhibitory Anti-Peroxidasin Antibodies in Pulmonary-Renal Syndromes.

BACKGROUND: Goodpasture syndrome (GP) is a pulmonary-renal syndrome characterized by autoantibodies directed against the NC1 domains of collagen IV in the glomerular and alveolar basement membranes. Exposure of the cryptic epitope is thought to occur via disruption of sulfilimine crosslinks in the NC1 domain that are formed by peroxidasin-dependent production of hypobromous acid. Peroxidasin, a heme peroxidase, has significant structural overlap with myeloperoxidase (MPO), and MPO-ANCA is present both before and at GP diagnosis in some patients. We determined whether autoantibodies directed against peroxidasin are also detected in GP. METHODS: We used ELISA and competitive binding assays to assess the presence and specificity of autoantibodies in serum from patients with GP and healthy controls. Peroxidasin activity was fluorometrically measured in the presence of partially purified IgG from patients or controls. Clinical disease severity was gauged by Birmingham Vasculitis Activity Score. RESULTS: We detected anti-peroxidasin autoantibodies in the serum of patients with GP before and at clinical presentation. Enriched anti-peroxidasin antibodies inhibited peroxidasin-mediated hypobromous acid production in vitro. The anti-peroxidasin antibodies recognized peroxidasin but not soluble MPO. However, these antibodies did crossreact with MPO coated on the polystyrene plates used for ELISAs. Finally, peroxidasin-specific antibodies were also found in serum from patients with anti-MPO vasculitis and were associated with significantly more active clinical disease. CONCLUSIONS: Anti-peroxidasin antibodies, which would previously have been mischaracterized, are associated with pulmonary-renal syndromes, both before and during active disease, and may be involved in disease activity and pathogenesis in some patients.

Effects of Traumatic Amputation on ß-Trace Protein and ß2-Microglobulin Concentrations in Male Soldiers.

BACKGROUND: Serum creatinine (SCr) levels are decreased following traumatic amputation, leading to the overestimation of glomerular filtration rate (GFR). ß-Trace protein (BTP) and ß2-microglobulin (B2M) strongly correlate with measured GFR and have not been studied following amputation. We hypothesized that BTP and B2M would be unaffected by traumatic amputation. METHODS: We used the Department of Defense Serum Repository to compare pre- and post-traumatic amputation serum BTP and B2M levels in 33 male soldiers, via the N Latex BTP and B2M nephelometric assays (Siemens Diagnostics, Tarrytown, N.Y., USA). Osterkamp estimation using DEXA scan measurements was used to establish percent estimated body weight loss (%EBWL). Results were analyzed for small (3-5.9% EBWL), medium (6-13.5%), and large (>13.5%) amputation subgroups; and for a control group matched 1:1 to the 12 large amputation subjects. Paired Student's t test was used for comparisons. RESULTS: Mean serum BTP levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. BTP appeared to decrease following large %EBWL amputation (p = 0.05). Mean serum B2M levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. B2M appeared to increase following large %EBWL amputation (p = 0.05). CONCLUSIONS: BTP and B2M levels are less affected than SCr by amputation, and should be considered for future study of GFR estimation. BTP and B2M changes following large %EBWL amputation require validation and may offer insight into non-GFR BTP and B2M determinants as well as increased cardiovascular disease and mortality following amputation.

Surgical intervention and long-term renal outcomes of congenital ureteropelvic junction obstruction in a young adult cohort.

PURPOSE: To evaluate the impact of surgical intervention on long-term renal outcomes for adult patients with congenital ureteropelvic junction obstruction (UPJO). METHODS: We queried service members diagnosed with UPJO from the United States Military Health System electronic health records from 2005 to 2020. We assessed demographic, laboratory, radiology, surgical intervention, and outcome data. We evaluated the impact of surgical intervention on renal function based on the estimated glomerular filtration rate (eGFR), hypertension (HTN, defined as any prescription for blood pressure [BP] medication and/or average of two BP readings ≥ 130/80 mmHg more than 2 weeks apart), and changes in renal excretory function on radionuclide scans. RESULTS: We identified 108 individuals diagnosed with congenital UPJO; mean follow-up of 7 years. Mean age at diagnosis was 25 years; 95% male; 69% White, 15% Black. At diagnosis, median BP was 130/78 mmHg and mean eGFR 93 ml/min/1.73m2. Subsequently, 85% had pyeloplasty and 23% had stent placement. There were no significant differences in mean eGFR pre- and post-intervention (94 vs. 93 ml/min/1.73m2, respectively; p = 0.15) and prevalence of defined HTN (59% vs. 61%, respectively; p = 0.20). Surgical intervention for right-sided UPJO significantly reduced the proportion of patients with delayed cortical excretion (54% pre vs. 35% post, p = 0.01) and T½ emptying time (35 min vs. 19 min, p = 0.009). Similar trends occurred with left-sided UPJO but were not significant. CONCLUSION: Surgical intervention was not associated with significant differences in the long-term outcomes of kidney function and HTN prevalence in our young adult cohort. However, renal excretory function improved on radionuclide scans.

Association of Race and Risk of Future Scleroderma Renal Crisis at Systemic Sclerosis Diagnosis.

OBJECTIVE: Scleroderma renal crisis (SRC) is a rare and severe manifestation of systemic sclerosis (SSc). Although it is well documented that Black patients with SSc have worse morbidity and mortality than non-Black patients, racial predilection for SRC is underreported. We examine the association of race and future development of SRC in an SSc cohort. METHODS: Using the electronic health record of the US Military Health System, we conducted a comprehensive chart review of each patient with SSc from 2005 to 2016. The final study cohort was comprised of 31 SRC cases and 322 SSc without SRC controls. We conducted logistic regression of SRC as the outcome variable and race (Black versus non-Black) as the primary predictor variable, adjusted for age, estimated glomerular filtration rate, hypertension, and proteinuria at SSc diagnosis. RESULTS: Of 353 patients, 294 had identifiable race (79 Black, 215 non-Black). Thirteen of 79 Black patients (16.5%) versus 16 of 215 (7.4%) non-Black patients developed SRC (P = 0.02). On adjusted analysis, Black patients had a significantly higher risk of developing SRC than non-Black patients (odds ratio 6.4 [95% confidence interval 1.3-31.2], P = 0.02). Anti-Ro antibody was present in a higher proportion of Black SRC patients versus Black patients without SRC (45% versus 14%, P = 0.01). Conversely, older age, thrombocytopenia, and anti-RNA polymerase III antibody at SSc diagnosis were significantly associated with future SRC in the non-Black cohort. CONCLUSION: Black race was independently associated with a higher risk of future SRC. Further studies are needed to elucidate the mechanisms that underlie this important association.

Asymptomatic autoantibodies associate with future anti-glomerular basement membrane disease.

The pathophysiology of anti-glomerular basement membrane (anti-GBM) disease before clinical presentation is unknown. The presence of anti-GBM, anti-proteinase 3 (PR3), and anti-myeloperoxidase (MPO) antibodies associate with the disease at the time of diagnosis, but little is known about the presence of these autoantibodies before diagnosis. We used serum samples from the Department of Defense Serum Repository to conduct a case-control study involving 30 patients diagnosed with anti-GBM disease and 30 healthy controls matched for the age, gender, race, and age of the serum samples. We analyzed a maximum of three samples from each subject: the most recent sample before diagnosis, the penultimate sample before diagnosis, and the oldest sample available; the average time between the most recent sample and diagnosis was 195 days (range, 4 to 1346 days). Elevated anti-GBM levels (≥3 U/ml) were present in four patients, all less than 1 year before diagnosis but in no controls. Detectable anti-GBM antibody levels (≥1 U/ml but <3 U/ml) in a single serum sample before diagnosis were more frequent in cases than controls (70% versus 17%, P < 0.001). Only study patients had detectable anti-GBM levels in multiple samples before diagnosis (50% versus 0%, P < 0.001). Almost all patients had detectable anti-PR3 and/or anti-MPO that preceded the onset of disease. Among patients with a clear antecedent antibody, anti-PR3 or anti-MPO always became detectable before the anti-GBM antibody. In summary, our data describe the subclinical formation of autoantibodies, which improves our understanding of the pathophysiology of anti-GBM disease.

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression.

Background: FSGS is a heterogeneic glomerular disease. Risk factors for kidney disease ESKD and the effect of immunosuppression treatment (IST) has varied in previously published cohorts. These cohorts were limited by relatively small case numbers, short follow-up, lack of racial/ethnic diversity, a mix of adult and pediatric patients, lack of renin-angiotensin-aldosterone system (RAAS) inhibition, or lack of subgroup analysis of IST. Methods: We compared demographics, clinical characteristics, histopathology, and IST to long-term renal survival in a large, ethnically diverse, adult cohort of 338 patients with biopsy-proven FSGS with long-term follow-up in the era of RAAS inhibition using data from the US Department of Defense health care network. Results: Multivariate analysis showed that nephrotic-range proteinuria (NRP), eGFR <60 ml/min per 1.73 m2, hypoalbuminemia, interstitial fibrosis and tubular atrophy, and interstitial inflammation at diagnosis and the absence of remission were all associated with worse long-term renal survival. IgM, C3, and a combination of IgM/C3 immunofluorescence staining were not associated with reduced renal survival. IST was not associated with improved renal survival in the whole cohort, or in a subgroup with NRP. However, IST was associated with better renal survival in a subgroup of patients with FSGS with both NRP and hypoalbuminemia and hypoalbuminemia alone. Conclusions: Our study suggests that IST should be reserved for patients with FSGS and nephrotic syndrome. It also introduces interstitial inflammation as a potential risk factor for ESKD and does not support the proposed pathogenicity of IgM and complement activation.

Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter.

INTRODUCTION: Among kidney transplant recipients (KTRs) with end-stage kidney disease (ESKD) due to atypical hemolytic uremic syndrome (aHUS), recurrence is associated with poor allograft outcomes. We compared graft and patient survival of aHUS KTRs with and without prophylactic/early use of eculizumab, a monoclonal antibody that binds complement protein C5, at the time of transplantation. METHODS: We conducted a retrospective cohort study using the United States Renal Data System. Out of 123 624 ESKD patients transplanted between January 1, 2008, and June 1, 2016, we identified 348 (0.28%) patients who had "hemolytic uremic syndrome" as the primary cause of ESKD. We then linked these patients to datasets containing the Healthcare Common Procedure Coding System (HCPCS) code for eculizumab infusion. Patients who received eculizumab prior to or within 30 days of transplant represented the exposure group. We calculated crude incidence rates and conducted exact logistic regression, adjusted for recipient age and sex, for the study outcomes of graft loss, death-censored graft loss, and mortality. We also estimated the average treatment effect (ATE) by propensity-score matching, to reduce the bias in the estimated treatment effect on graft loss. RESULTS: Our final study cohort included 335 aHUS KTRs (23 received eculizumab, 312 did not), with a mean duration of follow-up of 5.8 ± 2.7 years. There were no significant differences in baseline demographic and clinical characteristics between the eculizumab versus non-eculizumab group. Patients who received prophylactic/early eculizumab were less likely to experience graft loss compared with those who did not receive eculizumab (0% vs 20%, P = .02), with an adjusted odds ratio of 0.13 (P = .02). In the propensity-score-matched sample, the ATE (eculizumab vs non-eculizumab) was -0.20 (95% confidence interval [CI] = -0.25 to -0.15, P < .001); thus, treatment was associated with an average of 20% reduction in graft loss. There was no significant difference in the risk of death between the 2 groups. CONCLUSIONS: Although there was no significant difference in the risk of death, prophylactic/early use of eculizumab was significantly associated with improved graft survival among aHUS KTRs. Given the high cost of eculizumab, randomized controlled trials are much needed to guide prophylactic strategies to prevent graft loss.

INTRODUCTION: Chez les receveurs d'une greffe rénale (RGR) dont l'insuffisance rénale terminale (IRT) est due au syndrome hémolytique et urémique atypique (SHUa), la récidive est associée à de mauvais résultats d'allogreffe. Nous avons comparé la survie du greffon et des patients RGR-SHUa avec et sans administration prophylactique/précoce d'éculizumab, un anticorps monoclonal qui lie la protéine C5 du complément, au moment de la transplantation. MÉTHODOLOGIE: Nous avons mené une étude de cohorte rétrospective en utilisant le United States Renal Data System. Parmi les 123 624 patients atteints d'IRT transplantés entre le 1er janvier 2008 et le 1er juin 2016, nous avons répertorié 348 (0,28 %) patients présentant un « syndrome hémolytique urémique ¼ comme cause principale de l'IRT. Nous avons ensuite lié ces patients à des ensembles de données contenant le code du Healthcare Common Procedure Coding System (HCPCS) pour la perfusion d'éculizumab. Les patients ayant reçu de l'éculizumab avant l'intervention ou dans les 30 jours suivant la transplantation représentaient le groupe d'exposition. Nous avons calculé les taux bruts d'incidence et procédé à une régression logistique exacte, corrigée selon l'âge et le sexe du receveur, pour les résultats de l'étude concernant la perte du greffon, la perte du greffon censurée par le décès et la mortalité. Nous avons également estimé l'effet de traitement moyen (ETM) par appariement des scores de propension, afin de réduire le biais de l'effet estimé du traitement sur la perte du greffon. RÉSULTATS: Notre cohorte d'étude finale comprenait 335 patients RGR-SHUa (23 ayant reçu de l'éculizumab et 312 n'en ayant pas reçu) dont le suivi s'établissait à 5,8 ± 2,7 ans. Aucune différence significative n'a été observée entre les caractéristiques cliniques et démographiques initiales des deux groupes de sujets. Les patients ayant reçu de l'éculizumab prophylactique/précoce étaient moins susceptibles de subir une perte du greffon que ceux qui n'en avaient pas reçu (0 % vs 20 %; P = 0,02), avec un rapport de cotes corrigé de 0,13 (P = 0,02). Dans l'échantillon aux scores de propension appariés, l'ETM (éculizumab vs sans éculizumab) était de −0,20 (IC 95 %: −0,25 à −0,15; P < 0,001), le traitement a donc été associé à une réduction moyenne de 20 % de la perte du greffon. Aucune différence significative n'a été observée entre les deux groupes quant au risque de décès. CONCLUSION: Bien qu'aucune différence significative n'ait été observée pour le risque de mortalité, l'administration prophylactique/précoce d'éculizumab a été associée de façon significative à une amélioration de la survie du greffon chez les patients RGR-SHUa. Étant donné le coût élevé de l'éculizumab, des essais contrôlés randomisés sont nécessaires pour orienter les stratégies prophylactiques visant à prévenir la perte du greffon.

Aliskiren as an adjunct therapy for atypical hemolytic uremic syndrome.

Direct renin inhibitors (DRIs) block the activation of the alternative complement pathway in vitro and could be a treatment option for refractory hypertension in atypical hemolytic uremic syndrome (aHUS). A 20-year-old male presented with primary aHUS complicated by end-stage renal disease and refractory malignant hypertension despite being on five antihypertensive medications at maximum dose. Only a partial response was achieved with aliskiren and eculizumab, but after increasing aliskiren to a supratherapeutic dose, antihypertensive medication was reduced, platelets increased, C3 increased and epoetin alfa requirement decreased. DRI may be an adjunct treatment for malignant hypertension associated with aHUS.

Biotin supplement interference with immunoassays for parathyroid hormone and 25-hydroxyvitamin D in a patient with metabolic bone disease on maintenance hemodialysis.

Biotin (vitamin B7) is a dietary supplement that can lead to falsely abnormal endocrine function tests. The impact of biotin on both 25-hydroxyvitamin D [25(OH)D] and intact parathyroid hormone (iPTH) have not been previously described in end-stage renal disease (ESRD). A woman with ESRD on hemodialysis taking biotin 10 mg daily had a 25(OH)D spike from 25 to >100 ng/mL and an iPTH decrease from 966 to 63 pg/mL. After discontinuation of biotin, her 25(OH)D and iPTH returned to baseline. Biotin can cause erroneous 25(OH)D and iPTH results in ESRD that could adversely affect patient care.

Treatment for Severe Coronavirus Disease 2019 With the Seraph-100 Microbind Affinity Blood Filter.

To determine whether Seraph-100 (Exthera Medical Corporation, Martinez, CA) treatment provides clinical benefit for severe coronavirus disease 2019 cases that require mechanical ventilation and vasopressor support. DATA SOURCES: The first two patients in the United States treated with the novel Seraph-100 device. These cases were reviewed by the Food and Drug Administration prior to granting an emergency use authorization for treatment of coronavirus disease 2019. STUDY SELECTION: Case series. DATA EXTRACTION: Vasopressor dose, mean arterial pressure, temperature, interleukin-6, C-reactive protein, and other biomarker levels were documented both before and after Seraph-100 treatments. DATA SYNTHESIS: Vasopressor dose, temperature, interleukin-6, and C-reactive protein levels declined after Seraph-100 treatments. Severe acute respiratory syndrome coronavirus 2 viremia was confirmed in the one patient tested and cleared by the completion of treatments. CONCLUSIONS: Seraph-100 use may improve hemodynamic stability in coronavirus disease 2019 cases requiring mechanical ventilation and vasopressor support. These findings warrant future study of a larger cohort with the addition of mortality and total hospital day outcomes.

Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces proteinuria in patients with glomerular disease, although its impact on glomerular filtration rate (GFR) is unknown. We hypothesized that pentoxifylline would slow the estimated GFR decrease in patients with chronic kidney disease at high risk of progression. STUDY DESIGN: Pilot randomized double-blind placebo-controlled trial. SETTING & PARTICIPANTS: 40 outpatients with decreased GFR, hypertension, and proteinuria greater than 1 g/24 h currently treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the combination and followed up in a nephrology clinic at a tertiary medical care facility. INTERVENTION: Pentoxifylline, 400 mg twice daily, or matching placebo. OUTCOMES: Difference in rates of estimated GFR change during the 1-year study period between the 2 groups. MEASUREMENTS: Estimated GFR (4-variable Modification of Diet in Renal Disease Study equation) and proteinuria by 24-hour urine collection were assessed at baseline and 6 and 12 months after enrollment. RESULTS: Baseline characteristics were similar between the 2 groups. At 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (-1.2 +/- 7.0 versus -7.2 +/- 8.2 mL/min/1.73 m2/y; mean difference, -6.0 mL/min/1.73 m2/y; 95% confidence interval, -11.4 to -0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (-9.6 +/- 11.9 mL/min/1.73 m2/y; mean difference, -8.4 mL/min/1.73 m2/y; 95% confidence interval, -14.8 to -2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year. LIMITATIONS: Small sample size and incomplete follow-up. CONCLUSIONS: Pentoxifylline may slow the estimated GFR decrease in high-risk patients. This may be independent of its antiproteinuric properties and warrants further investigation.

Risk Factors for Future Scleroderma Renal Crisis at Systemic Sclerosis Diagnosis.

OBJECTIVE: Systemic sclerosis (SSc) is a disease of autoimmunity, fibrosis, and vasculopathy. Scleroderma renal crisis (SRC) is one of the most severe complications. Corticosteroid exposure, presence of anti-RNA polymerase III antibodies (ARA), skin thickness, and significant tendon friction rubs are among the known risk factors at SSc diagnosis for developing future SRC. Identification of additional clinical characteristics and laboratory findings could expand and improve the risk profile for future SRC at SSc diagnosis. METHODS: In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the demographics, clinical characteristics, and laboratory results at SSc diagnosis for 31 cases who developed SRC after SSc diagnosis to 322 SSc without SRC disease controls. RESULTS: After adjustment for potential confounding variables, at SSc diagnosis these conditions were all associated with future SRC: proteinuria (p < 0.001; OR 183, 95% CI 19.1-1750), anemia (p = 0.001; OR 9.9, 95% CI 2.7-36.2), hypertension (p < 0.001; OR 13.1, 95% CI 4.7-36.6), chronic kidney disease (p = 0.008; OR 20.7, 95% CI 2.2-190.7), elevated erythrocyte sedimentation rate (p < 0.001; OR 14.3, 95% CI 4.8-43.0), thrombocytopenia (p = 0.03; OR 7.0, 95% CI 1.2-42.7), hypothyroidism (p = 0.01; OR 2.8, 95% CI 1.2-6.7), Anti-Ro antibody seropositivity (p = 0.003; OR 3.9, 95% CI 1.6-9.8), and ARA (p = 0.02; OR 4.1, 95% CI 1.2-13.8). Three or more of these risk factors present at SSc diagnosis was sensitive (77%) and highly specific (97%) for future SRC. No SSc without SRC disease controls had ≥ 4 risk factors. CONCLUSION: In this SSc cohort, we present a panel of risk factors for future SRC. These patients may benefit from close observation of blood pressure, proteinuria, and estimated glomerular filtration rate, for earlier SRC identification and intervention. Future prospective therapeutic studies could focus specifically on this high-risk population.

Autoantibodies are present before the clinical diagnosis of systemic sclerosis.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disorder associated with vascular dysfunction and fibrotic changes in the skin, vasculature and internal organs. Although serologic abnormalities are an important diagnostic tool for SSc, little is known about whether autoantibodies precede clinical diagnosis. Here we investigated the presence of autoantibodies before SSc diagnosis and assessed whether certain autoantibodies might associate with the future onset of scleroderma renal crisis (SRC), a potentially fatal complication of the disease. Using the Department of Defense Serum Repository, autoantibodies were analyzed from archived, prospectively collected, longitudinal serum samples from sixteen individuals with SRC (SSc/SRC) and thirty cases of SSc without SRC (SSc/no SRC), matched for age, sex, and race. Seventy five percent (12/16) of the SSc/SRC and 40% (12/30) of the SSc/no SRC were seropositive for at least one autoantibody prior to clinical diagnosis (up to 27.1 years earlier, mean = -7.4 years). Although both disease groups demonstrated a heterogeneous immunoreactivity profile against the autoantigen panel, the SSc/SRC subjects showed two enriched clusters with one featuring elevated levels of autoantibodies against Ro52 and/or Ro60 and another with high levels of immunoreactivity against the RNA polymerase complex. Consistent with larger spectrum of immunoreactivity and the elevated levels of autoantibodies in SSc/SRC, the total response against the autoantigen panel from the last time point of the seropositive subjects revealed that the SSc/SRC cohort harbored higher antibody levels (p = 0.02) compared to SSc/no SRC. Overall, our findings demonstrate that relevant seropositive autoantibodies often precede the clinical diagnosis of SSc/no SRC and SSc/SRC.

Outcomes After Post-Traumatic AKI Requiring RRT in United States Military Service Members.

BACKGROUND AND OBJECTIVES: Mortality and CKD risk have not been described in military casualties with post-traumatic AKI requiring RRT suffered in the Iraq and Afghanistan wars. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective case series of post-traumatic AKI requiring RRT in 51 military health care beneficiaries (October 7, 2001-December 1, 2013), evacuated to the National Capital Region, documenting in-hospital mortality and subsequent CKD. Participants were identified using electronic medical and procedure records. RESULTS: Age at injury was 26±6 years; of the participants, 50 were men, 16% were black, 67% were white, and 88% of injuries were caused by blast or projectiles. Presumed AKI cause was acute tubular necrosis in 98%, with rhabdomyolysis in 72%. Sixty-day all-cause mortality was 22% (95% confidence interval [95% CI], 12% to 35%), significantly less than the 50% predicted historical mortality (P<0.001). The VA/NIH Acute Renal Failure Trial Network AKI integer score predicted 60-day mortality risk was 33% (range, 6%-96%) (n=49). Of these, nine died (mortality, 18%; 95% CI, 10% to 32%), with predicted risks significantly miscalibrated (P<0.001). The area under the receiver operator characteristic curve for the AKI integer score was 0.72 (95% CI, 0.56 to 0.88), not significantly different than the AKI integer score model cohort (P=0.27). Of the 40 survivors, one had ESRD caused by cortical necrosis. Of the remaining 39, median time to last follow-up serum creatinine was 1158 days (range, 99-3316 days), serum creatinine was 0.85±0.24 mg/dl, and eGFR was 118±23 ml/min per 1.73 m(2). No eGFR was <60 ml/min per 1.73 m(2), but it may be overestimated because of large/medium amputations in 54%. Twenty-five percent (n=36) had proteinuria; one was diagnosed with CKD stage 2. CONCLUSIONS: Despite severe injuries, participants had better in-hospital survival than predicted historically and by AKI integer score. No patient who recovered renal function had an eGFR<60 ml/min per 1.73 m(2) at last follow-up, but 23% had proteinuria, suggesting CKD burden.