Defining oliguria during cardiopulmonary bypass and its relationship with cardiac surgery-associated acute kidney injury.

BACKGROUND: While urine flow rate ≤0.5 ml kg-1 h-1 is believed to define oliguria during cardiopulmonary bypass (CPB), it is unclear whether this definition identifies risk for acute kidney injury (AKI) . The purpose of this retrospective study was to evaluate if urine flow rate during CPB is associated with AKI. METHODS: Urine flow rate was calculated in 503 patients during CPB. AKI in the first 48 h after surgery was defined by the Kidney Disease: Improving Global Outcomes classification. Adjusted risk factors associated with AKI and urine flow rate were assessed. RESULTS: Patients with AKI [n=149 (29.5%)] had lower urine flow rate than those without AKI (P<0.001). The relationship between urine flow and AKI risk was non-linear, with an inflection point at 1.5 ml kg-1 h-1 Among patients with urine flow <1.5 ml kg-1 h-1, every 0.5 ml kg-1 h-1 higher urine flow reduced the adjusted risk of AKI by 26% (95% CI 13-37; P<0.001). Urine flow rate during CPB was independently associated with the risk for AKI. Age up to 80 years and preoperative diuretic use were inversely associated with urine flow rate; mean arterial pressure on CPB (when <87 mmHg) and CPB flow were positively associated with urine flow rate. CONCLUSIONS: Urine flow rate during CPB <1.5 ml kg-1 h-1 identifies patients at risk for cardiac surgery-associated AKI. Careful monitoring of urine flow rate and optimizing mean arterial pressure and CPB flow might be a means to ensure renal perfusion during CPB. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00769691 and NCT00981474.

Renal biopsy in the management of lupus nephritis during pregnancy.

The differential diagnosis of proteinuria and hematuria in pregnancy is broad and includes active lupus nephritis. Identification of the correct diagnosis often has a profound therapeutic impact on not only the mother but also the fetus. To date, relatively few reports exist on the role of renal biopsy during pregnancy among women with systemic lupus erythematosus (SLE). We present a case series of 11 pregnant women with SLE who underwent a renal biopsy to evaluate a presumptive flare of lupus nephritis. The electronic medical record was retrospectively analyzed for pre-biopsy serum creatinine, proteinuria, hematuria, antinuclear antibodies (ANA), and antibodies to double-stranded DNA (anti-dsDNA); histologic findings on renal biopsy; and the clinical course of each mother and fetus. From 2001 to 2012, 11 pregnant women with SLE flares during pregnancy underwent a renal biopsy at an academic tertiary medical center. At the time of biopsy, median gestational age was 16 weeks (range 9 to 27), median serum creatinine was 0.6 mg/dl (interquartile range 0.5 to 0.9), six (55%) had hematuria, and all had proteinuria >500 mg/24 hours. Proliferative lupus nephritis was found in 10 (91%) of 11 biopsies (five with ISN/RPS Class III; five with ISN/RPS Class IV). All but one individual underwent a change in management guided by information gleaned from renal biopsy. No apparent biopsy-related complications occurred to mother or fetus. Three women elected to terminate their pregnancy; although many factors were involved, the findings on renal biopsy informed the decision-making process. Among the remaining cases, there were three pre-term deliveries, one fetus with complete heart block, one in utero demise, and one maternal death. Renal biopsy is helpful at informing the management of patients with lupus nephritis during pregnancy.

Hemodynamic and biochemical alterations in dogs with lymphoma after induction of chemotherapy.

BACKGROUND: Doxorubicin is a common antineoplastic agent with dose-dependent cardiotoxic adverse effects, and pre-existing myocardial dysfunction is a contraindication to its use. OBJECTIVES: To systematically define the hemodynamic and biochemical alterations in dogs undergoing chemotherapy for newly diagnosed lymphoma and assess the reversibility of these alterations with fluid administration. ANIMALS: Twenty-one client-owned dogs with newly diagnosed lymphoma were evaluated 1 week after induction of chemotherapy. Underlying degenerative valve disease was exclusionary. Eighteen healthy age- and weight-matched dogs were used as controls. METHODS: Physical examination, blood pressure by Doppler, echocardiography, and biochemical evaluation (routine serum biochemistry, plasma renin activity and aldosterone concentrations, plasma and urine osmolalities, and urine electrolyte concentrations) were measured in dogs with lymphoma and compared to controls. Dogs with lymphoma received crystalloids IV at 6 mL/kg/h for 24 hours. All variables were reassessed at 4 and 24 hours. Deuterium oxide dilution and bromide dilution were used to determine total body water and extracellular water space, respectively. RESULTS: Baseline echocardiograms showed significantly smaller chamber dimensions in dogs with lymphoma compared to controls. These changes were reversed by fluid administration. Systolic blood pressure and urine sodium concentration were significantly increased, and bromide dilution space, PCV, urine specific gravity, and urine potassium concentration were significantly decreased compared to controls. CONCLUSION AND CLINICAL IMPORTANCE: Echocardiographic and biochemical abnormalities in dogs with lymphoma appear consistent with volume depletion, and may be the result of systemic hypertension and subsequent pressure natriuresis.

Predictors of kidney biopsy complication among patients with systemic lupus erythematosus.

Kidney biopsy is essential for the diagnosis and management of lupus nephritis. The risk of bleeding complication, however, is not defined in the systemic lupus erythematosus population. A retrospective cohort study was conducted to determine predictors of major and minor complications among patients with systemic lupus erythematosus undergoing percutaneous ultrasound-guided kidney biopsy. Major complications included bleeding necessitating intervention, hypotension requiring vasopressors or higher level of care or death. Minor complications included moderate or large (≥ 4 cm in largest diameter) perinephric hematoma, gross hematuria or voiding difficulties. All patients were observed for at least 23 h post-procedure. The overall incidence of bleeding was 10.5% (2.7% major, 7.8% minor). Adjusted logistic regression showed that for every 10,000 cells/mm(3) decrease in platelet count, risk for major and any complication increased by 27% (odds ratio 1.27; 95% confidence intervals 1.06-1.51; p = 0.01) and 8% (odds ratio 1.08; 95% confidence intervals 1.02-1.15; p = 0.01), respectively. Patients with a platelet count <150,000 cells/mm(3) were 30 times more likely to experience a major complication (p = 0.002). Other candidate predictors, including steroid exposure, kidney function, hematocrit and histopathology, were not significant. Kidney biopsies are well tolerated in patients with systemic lupus erythematosus. However, patients with pre-biopsy platelet counts <150,000 cells/mm(3) are at markedly increased risk for a major bleeding complication.

Ritonavir-induced acute kidney injury: kidney biopsy findings and review of literature.

Ritonavir therapy is not generally considered nephrotoxic. We report a case of acute kidney injury secondary to ritonavir, with kidney biopsy demonstrating extensive acute tubular injury. This is the first report of a kidney biopsy and pathology in acute kidney injury associated with ritonavir. A review of published medical literature on the topic is also presented.

Hydroxychloroquine use predicts complete renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis.

The objective of this study was to identify clinical predictors of response to initial mycophenolate mofetil (MMF) therapy for membranous lupus nephritis (MLN). We observed the clinical outcomes of patients in the Hopkins Lupus Cohort within the first year of initiation of treatment with MMF therapy for newly diagnosed MLN, classified according to the new International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. Complete renal remission was defined as proteinuria less than 500 mg/24 hours. Demographic, clinical, treatment and laboratory data were examined for their association with renal remission. Twenty-nine MLN patients treated with MMF were identified. Eleven (38%) patients achieved complete renal remission by 12 months. Of those taking hydroxychloroquine, 7/11 (64%) were in remission within 12 months compared to only 4/18 (22%) of those not on hyroxychloroquine (P = 0.036 based on a log-rank test). This association persisted after controlling for the presence of anti-ds-DNA (P = 0.026). Our results provide evidence that hydroxychloroquine has a benefit for renal remission when MMF is used as the initial therapy for MLN. Although hydroxychloroquine is frequently stopped in patients with lupus nephritis, this study suggests it should be started or maintained.

Central nervous system lymphoma associated with mycophenolate mofetil in lupus nephritis.

Lymphomas, both within and outside the central nervous system, are uncommon among patients with systemic lupus erythematosus (SLE). We describe a 58-year old Korean woman with SLE who presented with acute headache and confusion in the setting of prednisone and mycophenolate mofetil (MMF) therapy used to treat focal proliferative and membranous lupus nephritis. Three-dimensional brain magnetic resonance imaging (MRI) showed two peripherally ('ring') enhancing lesions within the basal ganglia, bilaterally, with associated mass effect and subfalcine herniation. A brain biopsy revealed an Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma. This is the first description of CNS lymphoma in a patient treated with MMF for lupus nephritis. While intracerebral lymphoma in the immunocompromised patient with lupus is rare, this disorder should be considered in the differential diagnosis of new-onset neurological symptoms among such patients.

Chronic granulocytic leukemia in a dog.

A 4-year-old spayed dog had a recent history of increased WBC count and surgery for pyometra. Two weeks after surgery, WBC count was 57,640 cells/microliter; neutrophilia and immature myelocytic cells were detected. Histologic examination of liver and lymph node biopsy specimens revealed active granulopoiesis. Immature granulocytes that stained with chloroacetate esterase were evident. Bone marrow was excessively cellular and contained numerous granulocytes and blast cells. A diagnosis of chronic granulocytic leukemia was made on the basis of test results. Treatment with hydroxyurea returned the WBC count to reference range within 2 months. Mean survival time for dogs with chronic granulocytic leukemia is approximately 1 year; the dog of this report has remained healthy for more than 2 years. Chronic granulocytic leukemia is a rare neoplastic disease that must be differentiated from leukemoid inflammatory reactions. Although commonly described as a diagnosis determined by exclusion, diagnosis of chronic granulocytic leukemia should be made on the basis of specific criteria.

Surgical correction of late-onset Budd-Chiari-like syndrome in a dog.

An 18-month-old dog was examined because of ascites of 1 month's duration. Typical causes of ascites, including hepatic failure, heart failure, and protein-losing enteropathy, were ruled out. The dog's history included being hit by a car 6 months earlier, and the caudal vena cava had an S shape on thoracic radiographs. In addition, the abdominal fluid had a high protein concentration and low cellular content. These findings were all consistent with a diagnosis of postsinusoidal hypertension secondary to obstruction of hepatic venous outflow (Budd-Chiari-like syndrome). During exploratory thoracotomy, the pericardium appeared to have been torn from the heart and was partially wrapped around the caudal vena cava, causing a constriction. The pericardium was removed and the dog recovered without any further complications. Blunt trauma has been previously reported to cause kinking of the caudal vena cava and Budd-Chiari-like syndrome in dogs; but in these dogs, clinical signs of ascites developed a few days to several weeks after the traumatic incident. It appears that, depending on the cause of the hepatic venous outflow obstruction, onset of Budd-Chiari-like syndrome may be delayed for months.

Cellular chloride depletion inhibits cAMP-activated electrogenic chloride fluxes in HT29-18-C1 cells.

Cyclic AMP-activated chloride fluxes have been analyzed in HT29-18-C1 cells (a clonal cell line derived from a human colon carcinoma) using measurements of cell volume (electronic cell sizing), cell chloride content (chloride titrator) and intracellular chloride activity (6-methoxy-N-(3-sulfopropyl)quinolinium; SPQ). HT29-18-C1 was shown to mediate polarized chloride transport. In unstimulated cells, the apical membrane was impermeable to chloride and net chloride flux was mediated by basolateral furosemide-sensitive transport. Forskolin (10 microM) increased furosemide-insensitive chloride permeability of the apical membrane, and decreased steady-state intracellular chloride concentration approximately 9%. Cellular chloride depletion (substitution of medium chloride by nitrate or gluconate), caused greater than fourfold reduction in cellular chloride concentration. When chloride-depleted cells were returned to normal medium, cells regained chloride and osmolytes via bumetanide-sensitive transport, but forskolin did not stimulate bumetanide-insensitive chloride uptake. The inhibition of cAMP-activated chloride reuptake was not explained by limiting cation conductance, cell shrinkage, choice of substitute anion, or decreased generation of cAMP in chloride-depleted cells. When cells with normal chloride content were depolarized (135 mM medium potassium + 10 microM valinomycin), cAMP activated electrogenic chloride uptake permselective for Cl- approximately Br- > NO3- > I-. The electrogenic transport pathway was inhibited in chloride-depleted cells. Results suggest that chloride depletion limits activation of electrogenic chloride flux.