Acute Kidney Injury after Cardiac Surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CS-AKI) remains a vexing issue. Clinical trials for the prevention of CS-AKI have been disappointing despite enormous initial enthusiasm based on experimental data. SUMMARY: The schism in experimental and clinical data has triggered a relook at our understanding of CS-AKI and the experimental and preclinical models. In this review, we discuss the therapeutic targets of major clinical trials. KEY MESSAGES: The silver lining in the midst is the standardization of anesthetic and perioperative care proposed by national societies. Implementation of the KDIGO bundle is a reasonable option to decrease the incidence of CS-AKI despite lack of proven robust benefits.

My Kidney Is Fine, Can't You Cystatin C?

Background: Independent of age, sex, and body composition, individuals of African American race and individuals with high muscle mass have elevated serum creatinine (sCr) levels on average that may result in overestimation of chronic kidney disease (CKD). We present a misdiagnosed case of CKD based on sCr levels, illustrating the utility of cystatin C (CysC) confirmation testing to answer the question: Can confirmation screening of kidney function with CysC in African American patients and patients with high muscle mass reduce the misdiagnosis of CKD? Case Presentation: A 35-year-old African American man with a history of well-controlled HIV was found to have consistently elevated creatinine (Cr). We diagnosed CKD stage 3A based on the estimated glomerular filtration rate (eGFR). Further evaluation showed isolated elevation of sCr with unremarkable urinalysis and other laboratory tests. sCr elevation predated diagnosis and HIV treatment. A CysC-based eGFR (eGFRcys) test confirmed the absence of CKD. Conclusions: The 2009 CKD Epidemiology Collaboration calculation of eGFR based on sCr concentration uses age, sex, and race, with an updated recommendation in 2021 to exclude race. Both equations are less accurate in African American patients, individuals taking medications that interfere with sCr secretion and assay, and patients taking creatine supplements or high protein intake. These clinical scenarios decrease sCr-based eGFR (eGFRCr) but do not change measured eGFR or eGFRCys. Using sCr and serum cystatin C (eGFRCr-Cys) yields better concordance to measured eGFR across all races than does eGFR estimation based on Cr alone. Confirmation with CysC can avoid misdiagnosis, incorrect dosing of drugs, and inaccurate representation of the fitness for duty.

Goiter and Abdominal Mass: A Rare Presentation of Riedel's Thyroiditis.

Riedel's thyroiditis (RT) is a rare inflammatory autoimmune disease, often associated with various forms of systemic fibrosis such as sclerosing mesenteritis (SM). A woman in her late 30s presented with a diffusely enlarged firm goiter and a mesenteric mass complicated by biliary obstruction and hydronephrosis. Labs and thyroid ultrasound were consistent with autoimmune thyroiditis. Abdominal imaging demonstrated a mesenteric mass that encased mesenteric vessels and ureter. Flow cytometry and infectious workup were negative. Both thyroid and mesenteric biopsies revealed dense fibrosis with patchy lymphoplasmacytic aggregates, no evidence of carcinoma, lymphoma, or IgG4-related disease, which confirmed diagnoses of RT and SM. She improved clinically with steroids. The coincidental timing of thyroid enlargement and the mesenteric mass, and the similarity in histology suggest an association between RT and SM. Overall, the case highlights the challenges in diagnosing RT given its rarity and emphasises the importance of early treatment to prevent systemic involvement.

Prescribing patterns of SGLT-2 inhibitors for patients with heart failure: A two-center analysis.

Background: Sodium glucose co-transporter 2 inhibitors (SGLT2i) have been proven to reduce the combined risk of cardiovascular death and hospitalizations in patients with heart failure (HF), irrespective of the presence or absence of diabetes. Despite class 1 and class 2A recommendations for their usage in HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) respectively by the American College of Cardiology, their prescription rate has remained low. Objective: The aim of this study is to analyze SGLT2i prescription patterns at two academic institutions, with the goal of identifying barriers to implementation. Design: A two-center retrospective analysis was conducted on patients ≥18 years old with a diagnosis of heart failure who were admitted to one of two hospital systems between 5/1/21 and 5/31/22. Patients with an eGFR ≥20 mL/min/1.73m2 and BNP ≥ 100 pg/mL were included. Results: SGLT2i was prescribed in only 19 out of 1081 HFpEF patients (1.8 %) and 51 out of 1596 HFrEF patients (3.2 %). A majority of SGLT2i prescriptions for the HFpEF population came from general medicine services (57.9 %) after obtaining approval from a cardiologist, which was required at our institutions. Adverse effects such as hypoglycemia and urinary tract infections were not significantly associated with SGLT2i use. Conclusions: Despite proven benefits of this class of medications as witnessed in large-scale clinical trials, the implementation of this drug class continues to be low.

Not All Pulmonary Nodules in Smokers are Lung Cancer.

Diagnosis of pulmonary nodules requires an in-depth workup, including clinical evaluation, laboratory and pulmonary functions tests, and imaging, which helped to identify in this patient pulmonary rheumatoid arthritis, an important factor in patient mortality.

Natriuretic peptides in acute kidney injury - A sojourn on parallel tracks?

OBJECTIVE: The focus of this review was to elicit the mechanistic logic of the experimental and clinical study designs of natriuretic peptides (NP) in acute kidney injury (AKI) and to understand their respective outcomes. METHODS: Online search of PubMed and manual review of articles. Randomized trials, observational and physiologic studies of NPs and AKI were extracted. Rationale, design and study outcomes were analyzed. RESULTS: In experimental models of AKI, infusion of NP prevented post-ischemic fall in renal blood flow (RBF) or improvement in RBF, GFR, diuresis and natriuresis and demonstrated anti-inflammatory properties. NPs were most effective in the early stages of AKI, also in established phase of AKI but their effectiveness were limited to the time of infusion. Hypotension was a major side-effect. Based on these observations, preliminary clinical studies were performed which demonstrated improved urine output, RBF and GFR and reduced need for dialysis. However, randomized, controlled trials failed to demonstrate improvement in dialysis-free survival in different cohorts and study designs. Although NPs reduced the incidence of AKI in the postoperative period in cardiac surgery, it was not associated with improved long-term survival. In contrast to randomized trials, meta-analysis reported favorable results. CONCLUSIONS: Reasons for the divergence of experimental and clinical outcomes of NPs in AKI are discussed in this review article.

Long-term Use of Demeclocycline for the Treatment of Chronic Hyponatremia.

Syndrome of inappropriate antidiuretic hormone secretion may be a frequent accompaniment of aging without an obvious central nervous system or pulmonary disorder, tumor, or drugs as the confounding factor. Treatment is often warranted due to complex symptomatology that is often associated with unfavorable clinical outcomes. Although V2-receptor antagonists are effective in increasing serum sodium, their side-effect profile and cost may be a barrier to its use. We report a patient with symptomatic, severe, chronic hyponatremia requiring multiple hospitalizations, who was successfully maintained on long-term demeclocycline therapy.

Effects of Serum Uric Acid on Estimated GFR in Cardiac Surgery Patients: A Pilot Study.

BACKGROUND: The aim of the study was to investigate the effects of serum uric acid (SUA) on acute kidney injury (AKI) in patients undergoing cardiac surgery. METHODS: Prospectively collected data from a previous study were analyzed to investigate the relationship between SUA and AKI as assessed by neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine (SCr) and kinetic estimated glomerular filtration rate (KeGFR). RESULTS: Patients undergoing cardiovascular surgery (n = 37) were included. SUA was measured at postoperative 1 h. Statistically significant correlations were present between SUA and NGAL measured at postoperative 1 h (r = 0.39, p = 0.008), 6 h (r = 0.31, p = 0.029) and 24 h (r = 0.31, p < 0.001), respectively. Significant correlations were also noted between SUA and SCr measured on postoperative day 1 (r = 0.41, p = 0.006), day 2 (r = 0.29, p = 0.042) and day 3 (r = 0.42, p = 0.009). Negative correlations were demonstrated between SUA and day 1 (r = -0.44, p = 0.007), day 2 (r = -0.43, p = 0.007), day 3 (r = -0.44, p = 0.006 and day 4 KeGFR (r = -0.35, p = 0.035). The inverse relationship of SUA and KeGFR was also demonstrated with a different method (Jelliffe) of measurement. CONCLUSIONS: A reduction in glomerular filtration rate (GFR) can lead to a rise in SUA. However, in this study, we are able to show that SUA at 1 h (maximal dilution time) effectively predicts subsequent changes in urinary NGAL, SCr, KeGFR, and the development of AKI. Thus, these findings suggest that uric acid precedes and predicts acute changes in renal function and cannot be ascribed to a simple relationship in which a reduced GFR raises SUA.

Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery.

PURPOSE: Serum uric acid (SUA) is a novel risk factor for acute kidney injury (AKI), which adversely affects renal blood flow autoregulation, glomerular filtration rate (GFR), and promotes inflammation and angiogenesis. This pilot study investigated the effect of lowering SUA therapy on AKI, by using traditional and non-traditional markers. MATERIALS AND METHODS: In this prospective, double-blind, placebo-controlled, randomized pilot trial, 26 hyperuricemic patients undergoing cardiac surgery were randomized to receive rasburicase or placebo in the preoperative period. RESULTS: Subjects receiving rasburicase showed no difference in serum creatinine compared with the control group receiving placebo. Despite no difference in primary endpoint, the rasburicase group had less evidence of renal structural injury as reflected by urine neutrophil-associated lipocalin (uNGAL) concentrations, especially in subjects with higher SUA levels, more severe renal dysfunction (baseline GFR ≤ 45 mL/min/1.73 m(2)) or heart failure (left ventricular ejection fraction ≤45 %). CONCLUSIONS: In this study, rasburicase showed no benefit on postoperative serum creatinine in hyperuricemic subjects undergoing cardiac surgery. However, the observation that markers of structural renal injury such as uNGAL tended to be lower in rasburicase-treated subjects suggests potential different effects of uricase treatment on hemodynamic alterations in renal function versus structural mechanisms of kidney injury.

Post-operative serum uric acid and acute kidney injury.

BACKGROUND: We hypothesized that post-operative serum uric acid (SUA) may be associated with acute kidney injury (AKI). METHODS: In this prospective, observational study, the relationships between SUA, urine neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin-18 (uIL-18), serum monocyte chemoattractant protein-1 (sMCP-1) and tumor necrosis factor-alpha (sTNF-alpha), and incidence of AKI were determined. SUA were divided into tertiles and their association with AKI investigated. RESULTS: A total of 100 cardiac surgery patients were included for analyses. The 1st, 2nd, and 3rd SUA tertiles were associated with 15.1%, 11.7%, and 54.5% incidence of AKI, respectively. The 3rd SUA tertile, compared to the referent 1st tertile, was associated with an eightfold (OR 8.38, CI95% 2.13-33.05, p=0.002) increased risk for AKI. Patients with AKI on post-operative day 1 (n=11) were then excluded for the purpose of determining the predictive value of SUA to diagnose AKI on postoperative day 2 and during hospital stay. In comparison to the referent 1st tertile, the 3rd tertile SUA was associated with an eightfold increased risk for AKI on post-operative day 2 (adjusted OR 7.94, CI95% 1.50-42.08, P=.015) and a five-fold increased risk for AKI during hospital stay (OR 4.83, CI95% 1.21-19.20, P=.025), respectively. SUA (Area Under Curve, AUC 0.77 (CI95% 0.66-0.88, P<.001), serum creatinine (0.73, CI95% 0.62-0.84, P<.001) and sTNF-alpha (0.76, CI95% 0.65-0.87, P<.001) had the best diagnostic performance measured by the Receiver Operating Characteristics curves. CONCLUSIONS: We conclude that post-operative SUA is associated with an increased risk for AKI and compares well to conventional markers of AKI.

Fluid balance as an early indicator of acute kidney injury in CV surgery.

BACKGROUND: We hypothesized that positive fluid balance (FB) is the result of intraoperative kidney injury and associated renal vasoconstriction, and therefore may be an early clinical indicator of acute kidney injury (AKI). Since rapid changes in fluid volume occur during cardiovascular (CV) surgery, we investigated the influence of immediate postoperative FB on AKI. MATERIALS AND METHODS: Data from the Nesiritide Study were retrospectively analyzed to investigate the association between FB and AKI. RESULTS: Patients were classified into a negative FB (NegFB, median -1,221 ml, IQR -1,974 to -653 ml, n = 71) and a PosFB (median 849 ml, IQR 328 - 1,552 ml, n = 19) group based on FB status in the first 24 h postoperatively. The PosFB group had a higher incidence of AKI (NegFB 25.3% vs. PosFB 47.3%, p = 0.090) compared to the NegFB group. The difference in the incidence of AKI was significantly higher (NegFB 25.3% vs. high- PosFB 80%, p = 0.001) in the subset of patients who had FB ≥ 849 ml (highPosFB, n = 10). The highPosFB group demonstrated a significantly elevated risk for AKI in both unadjusted (OR = 9.8, 95% CI 1.9 - 51.2, p = 0.007) and multivariate models (OR = 8.1, 95% CI 1.5 - 45.1, p = 0.03). CONCLUSIONS: PosFB in the immediate postoperative period may be an independent early indicator of AKI in patients undergoing CV surgery.

Lowering serum uric acid to prevent acute kidney injury.

Epidemiological, experimental and clinical studies support a role for uric acid in acute kidney injury (AKI). We discuss how the conventional role of uric acid in AKI has now evolved from intratubular crystal deposition to pro-inflammatory, anti-angiogenic and immunological function. Data from recent studies are presented to support the hypothesis that uric acid may have a role in AKI via a crystal-independent process in addition to its traditionally accepted role to induce injury via crystal-dependent pathways.

Elevated uric acid increases the risk for acute kidney injury.

BACKGROUND: Uric acid has been proposed to play a role in acute kidney injury. We therefore investigated the potential influence of preoperative serum uric acid (SUA) on acute kidney injury in patients undergoing cardiovascular (CV) surgery. The primary aims were to investigate the incidence of acute kidney injury, peak serum creatinine (SCr) concentrations, hospital length of stay, and days on mechanical ventilation. METHODS: Retrospective study included patients who underwent CV surgery and had preoperative SUA available. Acute kidney injury was defined as an absolute increase in SCr ≥0.3 mg/dL from baseline within 48 hours after surgery. Univariate and multivariate logistic regression analysis was performed to determine the odds ratio for acute kidney injury. RESULTS: There were 190 patients included for analysis. SUA were divided into deciles. The incidences of acute kidney injury were higher with higher deciles of SUA. When the incidences of acute kidney injury were plotted against all available values of SUA at increments of 0.5 mg/dL, a J-shaped curve emerged demonstrating higher incidences of acute kidney injury associated with both hypo- and hyperuricemia. In the univariate analysis, SUA ≥5.5 mg/dL was associated with a 4-fold (odds ratio [OR] 4.4; 95% confidence interval [CI], 2.4-8.2), SUA ≥6 mg/dL with a 6-fold (OR 5.9; 95% CI, 3.2-11.3), SUA ≥6.5 mg/dL with an 8-fold (OR 7.9; 95% CI, 3.9-15.8), and SUA ≥7 mg/dL with a 40-fold (OR 39.1; 95% CI, 11.6-131.8) increased risk for acute kidney injury. In the multivariate analysis, SUA ≥7 mg/dL also was associated with a 35-fold (OR 35.4; 95% CI, 9.7-128.7) increased risk for acute kidney injury. The 48-hour postoperative and hospital-stay mean peak SCr levels also were higher in the SUA ≥5.5 mg/dL group compared with the SUA <5 mg/dL group. SUA ≥7 mg/dL was associated with increased length of hospital stay (SUA <7 mg/dL, 18.5 ± 1.8 days vs SUA ≥7 mg/dL, 32.0 ± 6.8 days, P = 0.058) and a longer duration of mechanical ventilation support (SUA <7 mg/dL, 2.4 ± 0.4 days vs SUA ≥7 mg/dL, 20.4 ± 4.5 days, P = 0.001). CONCLUSION: Preoperative SUA was associated with increased incidence and risk for acute kidney injury, higher postoperative SCr values, and longer hospital length of stay and duration of mechanical ventilation support in patients undergoing cardiac surgery. A J-shaped relationship appears to exist between SUA and acute kidney injury.

Practice implications of recent clinical trials for the prevention of acute kidney injury in cardiovascular surgery.

Acute kidney injury in patients undergoing cardiovascular surgery is a complex problem with associated increased risks for dialysis, short- and long-term mortality, and progression to end-stage renal disease. Interventions to prevent and treat renal complications in this cohort have seldom been uniformly satisfactory due to the differences in strategies for intervention, drug doses and duration of treatment, baseline renal functions, and population studied. Nonetheless, significant advances have been made and include recognition of the effect of preexisting organ dysfunction on renal outcomes, reassessment of existing therapeutic interventions, and exploration of the feasibility of newer agents to prevent and treat acute kidney injury in cardiovascular surgery patients. This article briefly reviews several of these issues with an emphasis on recent clinical trials in this cohort.

Long-term outcome of patients treated with prophylactic nesiritide for the prevention of acute kidney injury following cardiovascular surgery.

BACKGROUND: Previously, we reported that the prophylactic use of nesiritide did not reduce the incidence of dialysis or death following cardiovascular (CV) surgery despite reducing the incidence of acute kidney injury (AKI) in the immediate postoperative period. Therefore, we investigated whether the observed renal benefits of nesiritide had any long-term impact on cumulative patient survival and renal outcomes. METHODS: Participants of the Nesiritide Study, a previously reported prospective, double-blind, placebo-controlled, randomized clinical trial investigating the effect of nesiritide on the incidence of dialysis or death at 21 days in adult patients undergoing high-risk CV surgery, were included in the study. Data of the participants' most recent health and renal function status were obtained using institutional review board-approved patient questionnaires, medical records, and the database of the Social Security Administration. RESULTS: Data on all 94 patients from the Nesiritide Study were obtained. The mean follow-up period was 20.8 +/- 10.4 months. No differences in cumulative survival between the groups were noted at follow-up (nesiritide 77.7% vs placebo 81.6%, P = 0.798). Patients with in-hospital incidence of AKI had a higher rate of mortality than those with no AKI (AKI 41.4% vs no AKI 10.7%, P = 0.002). However, differences in survival time were not significant between the groups when the analysis was restricted to patients with AKI (nesiritide 16.8 +/- 4 months vs placebo 18.5 +/- 2.3 months, P = 0.729). CONCLUSIONS: Renoprotection provided by nesiritide in the immediate postoperative period was not associated with improved long-term survival in patients undergoing high-risk CV surgery.