Abstract Background A rhabdomyolysis protocol (RP) with mannitol and bicarbonate to prevent acute renal dysfunction (ARD, creatinine >2.0 mg/dL) remains controversial. Methods Patients with creatine ...kinase (CK) greater than 2,000 U/L over a 10-year period were identified. Shock, Injury Severity Score, massive transfusion, intravenous contrast exposure, and RP use were evaluated. RP was initiated for a CK greater than 10,000 U/L (first half of the study) or greater than 20,000 U/L (second half). Multivariable analyses were used to identify predictors of ARD and the independent effect of the RP. Results Seventy-seven patients were identified, 24 (31%) developed ARD, and 4 (5%) required hemodialysis. After controlling for other risk factors, peak CK greater than 10,000 U/L (odds ratio 8.6, P = .016) and failure to implement RP (odds ratio 5.7, P = .030) were independent predictors of ARD. Among patients with CK greater than 10,000, ARD developed in 26% of patients with the RP versus 70% without it ( P = .008). Conclusion Reduced ARD was noted with RP. A prospective controlled study is still warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Acute kidney injury (AKI) is rapidly increasing in global incidence and a healthcare burden. Prior maternal AKI diagnosis correlates with later pregnancy complications. As pregnancy influences ...developmental programming, we hypothesized that recovered parental AKI results in poor pregnancy outcomes, impaired fetal growth, and adult offspring disease.
Using a well-characterized model of rhabdomyolysis-induced acute kidney injury (RIAKI), a form of AKI commonly observed in young people, we confirmed functional renal recovery by assessing glomerular filtration rate (GFR) 2 weeks following RIAKI. We bred sham and recovered RIAKI sires and dams in timed, matched matings for gestational day (GD) 16.5 and offspring (birth-12 weeks, 6 months) study.
Despite a normal GFR pre-pregnancy, recovered RIAKI dams at GD16.5 had impaired renal function, resulting in reduced fetoplacental ratios and offspring survival. Pregnant RIAKI dams also had albuminuria and less renal megalin in the proximal tubule brush border than shams, with renal subcapsular fibrosis and higher diastolic blood pressure. Growth-restricted offspring had a reduced GFR as older adults, with evidence of metabolic inefficiency in male offspring; this correlated with reduced renal AngII levels in female offspring from recovered RIAKI pairings. However, the blood pressures of 6-month-old offspring were unaffected by parental RIAKI.
Our mouse model demonstrated a causal relationship among RIAKI, gestational risk, and developmental programming of the adult-onset offspring GFR and metabolic dysregulation despite parental recovery.
The international normalized ratio (INR) was developed to assess adequacy of Coumadin dosing. Its use has been generalized to guide fresh frozen plasma (FFP) therapy in stable patients. ...Thrombelastography (TEG) is a whole-blood assay measuring the viscoelastic properties of the clot in near real time. This study hypothesized that INR does not reflect coagulopathy and should not be used to guide FFP therapy in stable trauma and surgical patients.
Prospective observational data were collected from stable trauma and surgical patients (n = 106) who received FFP transfusions. Pretransfusion and posttransfusion blood samples were obtained to assess complete blood count, standard coagulation parameters (INR, partial thromboplastin time, fibrinogen and D-dimer), soluble clotting factors (II, V, VII, VIII, IX, X, XI, XII, proteins C and S) and TEG. Data were analyzed using a Mann-Whitney U-test. Significance was defined as p < 0.05.
A total of 262 U of FFP were transfused, with 78% of 106 patients receiving two or more units. Despite a reduction in INR, median TEG values remained within normal limits, while clotting factor levels retained adequate function to produce normal clotting before and following FFP transfusion.
The use of FFP in this population did not affect coagulation status in a clinically relevant manner based on TEG values and coagulation factor function. INR is not a predictor of coagulopathy and should not be used to guide coagulation factor replacement in stable trauma and surgical patients.
Diagnostic study, level III.
Cardiorenal syndrome type 1 (CRS‐1) acute kidney injury (AKI) is a critical complication of acute cardiovascular disease but is poorly understood. AKI induces acute albuminuria. As chronic ...albuminuria is associated with worsening kidney disease and albumin has been implicated in tubular epithelial injury, we investigated whether albumin participates in CRS‐1, and whether CRS‐1 alters renal albumin handling. We report the role of albumin in in vivo and in vitro CRS‐1 models. An established translational model, cardiac arrest and cardiopulmonary resuscitation (CA/CPR) induced severe acute albuminuria which correlated with tubular epithelial cell death. In vivo microscopy demonstrated CA/CPR‐induced glomerular filtration of exogenous albumin, while administration of exogenous albumin after CA/CPR worsened AKI compared to iso‐oncotic control. Increased albumin signal was observed in the proximal tubules of CA/CPR mice compared to sham. Comparison of albumin flux from tubular lumen to epithelial cells revealed saturated albumin transport within minutes of albumin injection after CA/CPR. In vitro, HK2 cells (human kidney tubular epithelial cells), exposed to oxygen‐glucose deprivation were injured by albumin in a dose dependent fashion. This interference was unchanged by the tubular endocytic receptor megalin. In conclusion, CRS‐1 alters albumin filtration and tubular uptake, leading to increased tubular exposure to albumin, which is injurious to tubular epithelial cells, worsening AKI. Our findings shed light on the pathophysiology of renal albumin and may guide interventions such as albumin resuscitation to improve CRS‐1 outcomes. This investigation may have important translational relevance for patients that receive exogenous albumin as part of their CRS‐1 treatment regimen.
Administered albumin worsens AKI in cardiorenal syndrome type 1; this is associated with increased albumin filtration and altered tubular albumin uptake.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract We reviewed 46 patients who underwent salvage hip arthroplasty (SHA) for revision of failed cannulated screws (CS), sliding hip screws (SHS), or intramedullary nails (IMN). The primary ...objective was to determine differences in operative difficulty. SHA after failed femoral neck fixation was associated with lower intra-operative demands than after failed peri-trochanteric fractures. Similarly, analysis by the index implant found that conversion arthroplasty after failed CSs was associated with lower intra-operative morbidity than failed SHSs or IMNs; differences between SHS and IMN were not as clear. Importantly, intra-operative data in cases of failed SHSs were similar regardless of the original fracture type, showing the device played a larger role than the fracture pattern. Complications and revision surgery rates were similar regardless of fracture type or fixation device. Our results suggest that operative demands and subsequent patient morbidity are more dependent on the index device than the fracture pattern during SHA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Identification of strategies to improve organ donor use remains imperative. Despite the association between hospital volume and outcomes for many common disease processes, there have been ...no studies that assess the impact of organ donor hospital volume on organ yield. Study Design A prospective observational study of all deceased organ donors managed by 10 organ procurement organizations across United Network for Organ Sharing regions 4, 5, and 6 was conducted from February 2012 to June 2015. To study the impact of hospital volume on organ yield, each donor was placed into a hospital-volume quartile based on the number of donors managed by their hospital. Stepwise logistic regression was used to identify the independent effect of hospital volume on the primary outcomes measure of having ≥4 organs transplanted per donor. Results Data from 4,427 donors across 384 hospitals were collected and hospitals were assigned quartiles based on their volume of deceased donors. Hospitals managed a mean ± SD of 3.3 ± 5.2 donors per hospital per year. After adjusting for age, ethnicity, donor type, blood type, BMI, creatinine, and organ procurement organization/donor service area, being managed in hospitals within the highest volume quartile remained a positive independent predictor of ≥4 organs transplanted per donor (odds ratio = 1.52; 95% CI, 1.29 to 1.79; p < 0.001). Conclusions Deceased organ donor hospital volume impacts organ yield, with the highest-volume centers being 52% more likely to achieve ≥4 organs transplanted per donor. Efforts should be made to share practices from these higher-volume centers and consideration should be given to centralization of donor care.
Abstract only Introduction: Acute cardiac injury with renal injury (acute cardiorenal syndrome) can induce chronic kidney disease (CKD), but mechanisms by which heart injury signals to kidney are ...unclear. Cardiac LIM protein (CSRP3) is a cardiomyocyte differentiation factor which is released into plasma after cardiac arrest. We assessed the hypothesis that CSRP3 induces myogenesis in the renal proximal tubule, inducing CKD. Methods: Two kidney injury models which result in similar acute kidney injury were tested, renal ischemia-reperfusion injury (IRI) or cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Seven weeks later, blood pressure (BP) and glomerular filtration rate (GFR; μg/min/100g) were measured, then mice were sacrificed. Single nucleus RNA sequencing (snRNAseq) was conducted on mouse kidney cells harvested 24h after CA/CPR. Primary human proximal tubular epithelial cells (hPTEC) were cultured from research-designated human kidneys. Recombinant CSRP3 (rCSRP3) was administered to hPTEC followed by RNAseq. Lastly, mice were injected with rCSRP3 after IRI, then sacrificed 7 weeks later. Results: CA/CPR (n=8) induced worse CKD than IRI (n=8) despite identical 24h GFR: GFR (CACPR 732.3+31.03 vs IRI 933.3+52.55, p<0.01); fibrosis (V aSMA /V kid ; CA/CPR 1.05±0.086 vs IRI 0.68±0.068, p<0.05); albuminuria (CACPR 0.032±0.005 mg vs IRI 0.132±0.026 mg, p<0.01). Compared with IRI, CA/CPR caused renovascular hypertrophy (thickness index; CACPR 0.75±0.038 vs IRI 0.49±0.011, p<0.01) and hypertension (BP ratio to sham: CACPR 1.22±0.029 vs IRI 0.98±0.069, p<0.01). SnRNAseq demonstrated that CA/CPR upregulated muscle cell differentiation ontologies in proximal tubule cells, driven by regulation of 110/162 myogenesis genes. In hPTEC, CSRP3 induced myogenesis differentiation factor 1 (MyoD1)>30 fold. CSRP3 injection in IRI mice resulted in lower GFR (CSRP3(+) 785.5±34.16 vs CSRP3(-) 954.2±55.69, p<0.05), and more renovascular hypertrophy (CSRP3(+) 0.61±0.011 vs CSRP3(-) 0.51±0.011, p<0.01, n=8/group) compared with IRI without CSRP3. Conclusions: CA/CPR caused CKD, renovascular hypertrophy, and hypertension associated with tubular myogenesis. CSRP3 induced myogenesis pathway in hPTEC and in mice. CSRP3 may drive cardiorenal-induced CKD.
In this study of three strategies — hypothermia, machine perfusion, or both — for pretransplantation preservation of kidneys from brain-dead donors, hypothermia was found to be inferior to machine ...perfusion.
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