Ganesh Kambhampati

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.

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.

Update on clinical trials for the prevention of acute kidney injury in patients undergoing cardiac surgery.

BACKGROUND Effective therapeutic agents for the prevention and treatment of acute kidney injury (AKI) after cardiac surgery remain elusive despite the tremendous advances in surgical techniques, technology, and understanding of disease processes. Recent developments and their effect on the incidence of AKI after cardiac surgery are discussed. DATA SOURCES Published clinical trials in PubMed, strength of evidence assessed by the guidelines of the American Family Physicians. CONCLUSIONS The definition of AKI has changed, and the focus of interventions has shifted from treatment to prevention to recovery from AKI. Antioxidants and biological agents have been added to classic armaments of hydration and diuretics in addition to tighter metabolic control to prevent AKI. Although the treatment options remain unsatisfactory, a lot of progress nevertheless continues to be made in the prevention and treatment 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.

Valacyclovir neurotoxicity can be effectively managed by hemodialysis.

Sir, Asahi et al. [1] recently reviewed the previously published cases of valacyclovir neurotoxicity (VAN) in your journal. They found a strong association between VAN and renal failure; all reported cases in the literature had some degree of renal dysfunction. Whilst the majority of these patients were receiving maintenance hemodialysis for end-stage renal disease (ESRD), there are only few reports on the correlation between changes in serum levels of valacyclovir and neurological status of the patient with regards to this modality of renal replacement therapy [2,3]. A 49-year-old woman with a history of ESRD on maintenance hemodialysis for 3 years was diagnosed with shingles of the left T4 dermatome. She was prescribed valacyclovir 1000 mg three times a day. After a total dose of 4000 mg, the patient was noted to be disoriented, confused, agitated, and hallucinating. On presentation to the emergency department, blood pressure was 170/85 mmHg, pulse 110, and temperature 36.7 C. She was found to be delirious, incoherent, oriented only to self, and following simple brief commands. There was no nuchal rigidity, reflexes were 1+ symmetrical, and she had no focal neurological deficits. Laboratory studies were unremarkable except for high blood urea nitrogen and creatinine and non-contrasted CT scan of the brain did not reveal any acute changes. VAN was suspected based on the history of recent initiation of valacyclovir, of which the dose was not adjusted for the degree of renal function. A serum valacyclovir level of 7.4 mcg/ml (normal: 2–4 mcg/ml) supported the diagnosis (measured via high-pressure liquid chromatography). The medication was stopped and the decision was made for emergent hemodialysis using a high-flux filter for two consecutive sessions of 4-h duration, separated by 12 h. The serum valacyclovir level decreased to 1.6 mcg/ml after the first hemodialysis treatment. Interestingly, the patient s mental status significantly improved in the middle of the second session and returned to baseline by the end of the treatment; the serum level of valacyclovir was found to be 0.83 mcg/ml at that time and did not rebound afterward (Fig. 1). Valacyclovir is the prodrug for acyclovir and is generally considered safe and efficacious. Administration of valacyclovir results in a twofold higher bioavailability compared with oral acyclovir. It is eliminated primarily by the kidneys through both glomerular filtration and tubular secretion. Therefore, the half-life of the drug is significantly prolonged in the presence of renal failure, increasing the possibility of serious adverse effects such as neurotoxicity. VAN includes a wide spectrum of neuropsychiatric disturbances ranging fromdizziness to coma [1]. Because the drug is readily dialyzable, high-flux and high-efficiency hemodialysis will provide rapid clearance of the drug. This observation adds to the previously published reports suggesting the role of hemodialysis in significant reduction in serum valacyclovir levels and improvement in symptoms [1,3]. We propose that only adjusted dose of valacyclovir should cautiously be used in patients with renal dysfunction, and that hemodialysis represents an efficient management strategy for rapid elimination of the drug in the setting of VAN.

Nonobstructive hydronephrosis due to social polydipsia: a case report

IntroductionExcessive fluid intake can lead to water intoxication, electrolyte abnormalities, exacerbation of heart failure and anatomical changes in the urinary tract that may present diagnostic and therapeutic challenges for patients and physicians. Although the development of nonobstructive hydronephrosis is recognized in patients with central and nephrogenic diabetes insipidus, pregnancy or psychiatric polydipsia, it is rarely a diagnostic consideration in healthy individuals with excessive fluid ingestion. We now present what we believe to be the first report of nonobstructive hydronephrosis associated with social polydipsia.Case presentationA 53-year-old African-American woman with moderate back pain was found to have bilateral moderate hydronephrosis and hydroureter by abdominal computed tomography. She underwent ureteral stent placement followed by exploratory laparoscopy with lysis of adhesions and a right oophorectomy, without resolution of the nonobstructive hydronephrosis. A careful assessment revealed a social habit of consuming approximately 5.5L of fluid daily in an effort to remain hydrated in accordance with public health service announcements. It was recommended that the patient reduce her fluid intake. A repeat ultrasound after six weeks revealed complete resolution of the bilateral hydronephrosis and hydroureter.ConclusionRecognition of the nonobstructive nature of hydronephrosis caused by polydipsia in healthy individuals is important to prevent unnecessary interventions.

Anaerobic clavicular osteomyelitis following colonoscopy in a hemodialysis patient

Patients on dialysis are immunocompromised and are therefore susceptible to both common and unusual infectious complications. These infections are often related to their dialysis access but even routine diagnostic tests unrelated to dialysis can also lead to rare adverse events. We present an unusual case of clavicular osteomyelitis from Bacteroides fragilis in a patient on maintenance hemodialysis following colonoscopy. The risk factors for this unusual site of infection, the incidence and guidelines for prophylactic antibiotic administration are discussed here.