Bhagwan Dass

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.

A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome

Tumour lysis syndrome (TLS) is a complication associated with the treatment of tumour types with high proliferative rate, large tumour burden or high sensitivity to cytotoxic therapy. The implementation of risk stratification strategies [1], appropriate prophylactic measures, vigilant monitoring of laboratory parameters and active interventions to reduce risk factors has dramatically decreased the incidence of clinically significant morbidity that results in end organ damage and mortality. Despite these advances, 5–6% of atrisk paediatric and adult patients undergoing chemotherapy develop acute kidney injury (AKI), and 40–50% of these patients will require dialysis therapies with associated allcause mortality in excess of 50% [2–4]. Similar outcomes are reported with spontaneous TLS [5]. The lack of standardized definitions and outcome measures has hampered appreciation of the extent of adverse renal outcomes in TLS. Recent adoption of a uniform definition of AKI (increase in serum creatinine of 0.3 mg/dL from baseline or a 50% increase in serum creatinine from baseline values within 48 h) [6] and the recognition that the development of in-hospital AKI have significant implications for long-term mortality [7] underscores the need to understand the mechanisms involved in AKI associated with TLS. Furthermore, the effect of chronic kidney disease (CKD) on renal outcomes in TLS requires a study, as clinical tumour lysis occurs more frequently in patients with pretreatment renal impairment [8]. One study examining risk factors for in-hospital AKI of diverse aetiologies reported that CKD increases the risk of AKI 40-fold with a 20-fold increased risk for dialysis [9]. Here, we will briefly review the current understanding of the pathogenesis of TLS-induced AKI. In particular, a recent literature suggests that AKI and nephropathy are not simply due to intrarenal crystal deposition of urate and phosphate. Mechanism of AKI associated with intrarenal deposition of uric acid crystals TLS is a group of metabolic complications that occur after the treatment of large volume, rapidly proliferating haematological cancers including not only acute leukaemia and aggressive lymphomas but also some solid tumours. Metabolic alterations that result include hyperkalaemia, hyperphosphataemia, hyperuricaemia and hyperuricosuria, hypocalcaemia and consequent AKI. Specifically, AKI associated with TLS has been considered to be exclusively a crystal-dependent process caused by the massive and abrupt release of intracellular metabolites from chemosensitive, rapidly proliferating tumour cells that undergo rapid lysis and release nucleic acid breakdown products, phosphorus and potassium. Both urate and calcium phosphate crystals may cause crystal-dependent injury of the kidney which overwhelms the normal homeostatic mechanism(s) autoregulating normal renal physiology [10]. One of the most important mediators of AKI resulting from TLS is uric acid. When dying cells release DNA and RNA, they are degraded in the liver and other sites with the rapid production of uric acid. Serum uric acid rises acutely, resulting in marked uricosuria. Such cell death and degradation also results in acid generation, often with volume depletion, resulting in acidic urine that decreases the solubility of uric acid. When levels of urinary uric acid exceed its solubility, both micro- and macrocrystal formations occur in the distal tubules and collecting ducts with obstruction of the tubular lumen. The prevention of AKI resulting from TLS includes initiating prophylactic measures prior to and during chemotherapy, including hydration, alkalinization of the urine, use of the xanthine oxidase inhibitor allopurinol, as well as the urate oxidase inhibitor, rasburicase or its derivatives.

Tuberculosis of the spine (Pott's disease) presenting as ‘compression fractures’

Study design: Case reports and survey of literature.Objective: Case reports of two women with tuberculosis (TB) of the spine (Potts disease) presenting with severe back pain and diagnosed as compression fracture are described. Physicians should include Potts disease in the differential diagnosis when patients present with severe back pain and evidence of vertebral collapse.Setting: Ohio, USAMethods: A review of the literature on the pathogenesis, pathophysiology, clinical presentation, diagnostic methods, treatment and prognosis of spinal TB was conducted.Results: After initial delay, proper diagnosis of spinal TB was made in our patients. Microbiologic diagnosis confirmed M. tuberculosis, and appropriate medical treatment was initiated.Conclusions: Although uncommon, spinal TB still occurs in patients from developed countries, such as the US and Europe. Back pain is an important symptom. Vertebral collapse from TB may be misinterpreted as ‘compression fractures’ especially in elderly women. Magnetic resonance imaging scan (MRI) is an excellent procedure for the diagnosis of TB spine. However, microbiologic diagnosis is essential. Mycobacterium tuberculosis may be cultured from other sites. Otherwise, biopsy of the spine lesion should be done for pathologic diagnosis, culture and stain for M. tuberculosis. Clinicians should consider Potts disease in the differential diagnosis of patients with back pain and destructive vertebral lesions. Proper diagnosis and anti-tuberculosis treatment with or without surgery will result in cure.

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.

Paradigm shift in the role of uric acid in acute kidney injury.

It has been known for decades that uric acid causes acute kidney injury by intratubular crystal precipitation and obstructing the renal tubules. Uric acid crystals stimulate inflammation and elicit immune responses in many disease conditions, including gouty arthritis. More recently, soluble uric acid has been reported to stimulate proliferation of vascular smooth muscle cells, inhibit endothelial function, cause renal vasoconstriction, impair renal blood flow autoregulation, and induce inflammatory response via crystal-independent mechanisms. This article examines the changing role for uric acid in acute kidney injury.

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.

Long-term Outcome of Patients Treated With Prophylactic Nesiritide for the Prevention of Acute Kidney Injury Following Cardiovascular Surgery

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.

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.

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.

Intra-abdominal hypertension can be monitored with femoral vein catheters during CRRT and may cause access recirculation.

OBJECTIVES Intra-abdominal hypertension (IAH) is an increasingly recognized disorder, and its diagnosis depends on accurate pressure monitoring. Bladder-based protocols are favored, but are not always clinically feasible. Abdominal venous (i.e. vena cava) pressure measurements are an alternative but are logistically challenging. We hypothesized that for patients suffering acute kidney injury, transducers built into renal replacement therapy (RRT) machines offer a simple opportunity to monitor pressures using catheters inserted via femoral veins. DESIGN We performed in vitro testing of the accuracy of pressure transducers incorporated into continuous RRT devices, using highly calibrated instrumentation in the IAH-relevant range of 0 to +50 mmHg. We developed a protocol for using this modality in vivo, by stopping all pumps so as to allow equilibration of pressures: clinical application in a patient with femoral vein catheters and IAH was then described. RESULTS In vitro analyses showed accuracy of the extracorporeal pressure transducers with an r² of 0.998, p < 0.001. In the patient case, the pressure transduced at the RRT device was identical to those obtained from bladder catheters. IAH also led to access recirculation and ineffective therapy. CONCLUSIONS Pressure sensors incorporated into continuous RRT machines can be accurate in the IAH physiologic range, and thus may be used to easily measure intra-abdominal pressure via appropriate-length femoral vein-inserted access catheters. If not relieved, IAH can be an under-appreciated cause of access recirculation and ineffective clearance for any RRT modality (continuous or intermittent) using femoral catheters.