Acute cortical necrosis in Falciparum malaria: an unusual manifestation.

The spectrum of acute renal failure in Falciparum malaria varies from mild urinary abnormalities to acute renal failure. Acute tubular necrosis has been reported in 1% patients, and acute cortical necrosis has rarely been reported. We present a case of acute cortical necrosis in a young patient with Falciparum malaria who had a prolonged oligo-anuric course followed by partial recovery of renal function.

How Robust are our Methods of Detecting Impaired Glomerular Filtration Rate in the Intensive Care Unit?

BACKGROUND: Serum creatinine is not a sensitive marker to assess early loss of renal function in acute kidney injury. Timed creatinine clearance and several formula used to predict glomreular filtration rate have not been validated. METHODS: In a prospective observational study in 50 adult patients admitted to the intensive care unit with apparent normal renal function, we assessed the glomerular filtration rate by the formula methods and timed creatinine clearance. RESULT: The mean serum creatinine was 0.77mg/dl, SD ± 0.15 (range 0.5-1.14 mg/dl). The mean measured creatinine clearance was 87.15 ml/min/1.73m(2), SD ± 20.5 (range 56.9-137 ml/min/1.73m(2)). In 25 (50%) patients, one hour urinary creatinine clearance was <80 ml/min/1.73m(2) and in two (4%) patients, the creatinine clearance was <60 ml/min/1.73m(2). Spearman correlation coefficient and regression analysis revealed a statistically significant correlation for the Cockcroft-Gault and predictive equations when compared with measured creatinine clearance. The differences between the predictive equations and creatinine clearance, as illustrated by the ±95% confidence interval in the Bland-Altman graphs was very significant [Cockcroft- Gault = -40.3 to 17.7 ml/min/ 1.73m(2), Modification of Diet in Renal Disease equation = -46.2 to 30.6 ml/min/1.73m(2) and the simplified Modification of Diet in Renal Disease equation = -72.8 to 24.8 ml/min/1.73m(2)]. CONCLUSION: Formula methods and creatinine clearance are more sensitive than serum creatinine in detecting early phase of acute kidney injury. However, there is no agreement between these methods of glomerular filtration rate estimation.

Successful medical treatment of emphysematous pyelonephritis in a renal allograft recipient.

Emphysematous pyelonephritis in renal allograft recipients is a rare but serious complication. The management of this entity is a subject of controversy in live related donor programs where the absence of a second donor is a key factor influencing surgical removal of the graft. We present a case of emphysematous pyelonephritis in a renal allograft recipient managed successfully with medical therapy alone.

Hepatitis C virus-related fibrosing cholestatic hepatitis in a renal transplant recipient.

Fibrosing cholestatic hepatitis (FCH) is a severe and progressive form of liver dysfunction seen in organ transplant recipients and immunosuppressed patients; it is usually associated with hepatitis B virus infection. We report 36-year-old man, a renal transplant recipient, also developed FCH with hepatitis C virus infection and succumbed to it.

Impact of hepatitis C virus infection in renal transplant recipients.

OBJECTIVES: The impact of hepatitis C virus (HCV) infection on the success of renal transplant is controversial. We assessed the effect of HCV infection on graft and patient survival in renal allograft recipients. METHODS: We retrospectively analyzed medical records of renal allograft recipients who were transplanted between June 1990 and March 2004. Patients were divided into those positive and negative for anti-HCV antibody. Graft and patient survival were compared between the groups. RESULTS: Of 126 patients studied (median age 34.5 years, range, 16-60; 111 men), 35 were positive for anti-HCV antibody. In seven patients, the antibodies were detected for the first time after renal transplant. Mean patient and graft survival duration in the anti-HCV negative group was longer (55 [SD 2] months [95% CI, 51-58]) than in the anti-HCV positive group (50 [SD 4] months [95% CI, 43-58]) (p< 0.05). Twenty-two patients died - 8 (22.8%) in the anti-HCV positive group and 14 (15.3%) in the negative group. In the anti-HCV positive group, infections were the cause of death in 5 patients and 3 patients died of liver cell failure. In the anti-HCV negative group, corresponding figures were 13 and one. CONCLUSION: HCV infection is a bad prognostic indicator for patient and graft survival duration in renal transplant recipients. Infections are the commonest cause of death in renal transplant recipients.

Salvia miltiorrhiza water-soluble extract, but not its constituent salvianolic acid B, abrogates LPS-induced NF-kappaB signalling in intestinal epithelial cells.

Herbal medicine has become an increasing popular therapeutic alternative among patients suffering from various inflammatory disorders. The Salvia miltiorrhizae water-soluble extract (SME) have been shown to possess antioxidant and anti-inflammatory properties in vitro. However, the mechanism of action and impact of SME on LPS-induced gene expression is still unknown. We report that SME significantly abrogated LPS-induced IkappaB phosphorylation/degradation, NF-kappaB transcriptional activity and ICAM-1 gene expression in rat IEC-18 cells. Chromatin immunoprecipitation assay demonstrated that LPS-induced RelA recruitment to the ICAM-1 gene promoter was inhibited by SME. Moreover, in vitro kinase assay showed that SME directly inhibits LPS induced IkappaB kinase (IKK) activity in IEC-18 cells. To investigate the physiological relevance of SME inhibitory activity on NF-kappaB signalling, we used small intestinal explants and primary intestinal epithelial cells derived from a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-kappaB cis-elements (cis-NF-kappaB(EGFP)). SME significantly blocked LPS-induced EGFP expression and IkappaBalpha phosphorylation in intestinal explants and primary IECs, respectively. However, salvianolic acid B, an activate component of SME did not inhibit NF-kappaB transcriptional activity and IkappaB phosphorylation/degradation in IEC-18 cells. These results indicate that SME blocks LPS-induced NF-kappaB signalling pathway by targeting the IKK complex in intestinal epithelial cells. Modulation of bacterial product-mediated NF-kappaB signalling by natural plant extracts may represent an attractive strategy towards the prevention and treatment of intestinal inflammation.

Routine Cyclosporine concentration - C2 level Monitoring. Is it helpful during the early post Transplant Period?

BACKGROUND: Pre dose or trough blood cyclosporine (CSA) concentration is routinely monitored and the result is used to alter patient's drug dosing. Patients with identical pre dose blood CSA may have very different systemic exposure to the drug. Recently CSA 2 hour post dose level [C2] has been reported to correlate better with drug exposure. We undertook this study to evaluate the influence of trough and C2, CSA concentration monitoring on short-term renal allograft outcomes. METHODS: 25 patients of renal transplant receiving a triple drug regimen of CSA micro emulsion (Panacea Biotec) 8mg/kg, azathioprine 1mg/kg and prednisolone 0.5mg/kg were analyzed prospectively for graft outcomes. CSA levels were monitored in whole blood by radioimmunoassay using monoclonal antibodies, at 72 hours after the transplant. RESULTS: The mean age of patients was 37.08 + 9.1 years. There were 20 males and 5 females. The mean age of donors was 40.2 + 8.2 years. There were 11 related donors with at least a haplomatch, 4 spousal and 10 unrelated donors with a nil antigen match. The mean pre dose CSA concentration was 289.22 + 171.9ng/ml; range (98.8 + 783.41ng/ml). The CSA concentration at 2 hours after the CSA administration was 838 + 310.87ng/ml (range, 169 + 1268ng/ml). 3 (12%) patients had acute rejection. In these patients the mean pre dose CSA concentration was 328.67ng/ml and the mean C2, CSA concentration was 1006.26ng/ml. CSA induced hemolytic uraemic syndrome was diagnosed in one patient. The trough and C2, CSA concentration levels were 174 and 870.83ng/ml respectively in this patient. CONCLUSION: In our study CSA levels, trough and peak showed significant inter patient variability. The trough and C2 concentration levels did not correlate with the episodes of acute rejection. We conclude that in a triple drug regimen with fixed dosing schedules routine trough CSA level monitoring is not helpful in the acute post renal transplant period.

Role of Ambulatory Blood Pressure Measurement in Diagnosis and Control of Hypertension.

Office blood pressure (BP) measurements by sphygmomanometer are not necessarily representative of patient's usual blood pressure. In contrast, ambulatory blood pressure measurements (ABPM) represent a large number of readings and may reflect the actual BP status of an individual. In this study, 150 individuals were studied in 2 groups. 110 patients (group A) had stage I & II, hypertension based on casual BP readings. 26 (23.6%) of them were found to be normontensive as per existing ABPM standard. There were 40 patients with poorly controlled hypertension on multiple drugs (group B). The trough/peak ratio of > 50% was seen in 12.5% of these patients at start of study. This increased to 84.8% after modification of drugs as per the profile on ABPM, thus indicating usefulness in achieving a smoother control.

Cardiac arrhythmias and silent myocardial ischemia during hemodialysis.

Cardiac arrhythmias are noted in a significant proportion of chronic renal failure (CRF) patients on hemodialysis (HD), and may contribute to cardiovascular mortality. A number of factors have been implicated in the genesis of these arrhythmias. The role of silent myocardial ischemia (SMI), however, has not been evaluated systematically. We prospectively studied 38 unselected CRF patients on regular HD by continuous Holter monitoring starting 24 hours before HD, lasting through the dialysis session and continued for 20 hours thereafter. The recordings were analyzed for frequency, timing and severity of supraventricular and ventricular arrhythmias and SMI as identified by ST-segment depression. Ventricular arrhythmias during HD were noted in 11 (29%) patients (group I), and were potentially life-threatening (Lown Class III and IVa) in 13%. The remaining 27 patients (group II) had no ventricular arrhythmias during HD. There was no difference in the age, sex ratio, duration of HD, blood pressure, fluctuations in weight, hematocrit, predialysis creatinine, sodium, potassium, calcium or inorganic phosphate levels between patients in the two groups. The number of patients with clinical ischemic heart disease was significantly greater in group I. SMI was noted in 72% and 33% of group I and II patients respectively (p = 0.026). 46% of those with and 25% of those without ST changes during HD developed ventricular arrhythmias during HD. Both SMI and ventricular arrhythmias were noted most frequently during the last hour of dialysis. Hypertension, diabetes mellitus and ischemic heart disease were observed more frequently amongst patients with SMI. Ventricular arrhythmias are detected in a significant proportion of CRF patients on HD. These are probably related to coronary artery disease since silent myocardial ischemia is also noted more frequently during HD in these patients. Further studies incorporating coronary angiography are needed in a larger number of patients to establish a definite causal relationship.

Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity.

NF-kappa B plays a critical role in the transcriptional regulation of proinflammatory gene expression in various cells. Cytokine-mediated activation of NF-kappa B requires activation of various kinases, which ultimately leads to the phosphorylation and degradation of I kappa B, the NF-kappa B cytoplasmic inhibitor. The food derivative curcumin has been shown to inhibit NF-kappa B activity in some cell types. In this report we investigate the mechanism of action of curcumin on cytokine-induced proinflammatory gene expression using intestinal epithelial cells (IEC). Curcumin inhibited IL-1 beta-mediated ICAM-1 and IL-8 gene expression in IEC-6, HT-29, and Caco-2 cells. Cytokine-induced NF-kappa B DNA binding activity, RelA nuclear translocation, I kappa B alpha degradation, I kappa B serine 32 phosphorylation, and I kappa B kinase (IKK) activity were blocked by curcumin treatment. Wound-induced p38 phosphorylation was not inhibited by curcumin treatment. In addition, mitogen-activated protein kinase/ERK kinase kinase-1-induced IL-8 gene expression and 12-O-tetraphorbol 12-myristate 13-acetate-responsive element-driven luciferase expression were inhibited by curcumin. However, I kappa B alpha degradation induced by ectopically expressed NF-kappa B-inducing kinase or IKK was not inhibited by curcumin treatment. Therefore, curcumin blocks a signal upstream of NF-kappa B-inducing kinase and IKK. We conclude that curcumin potently inhibits cytokine-mediated NF-kappa B activation by blocking a signal leading to IKK activity.