Acute renal allograft rejection following pegylated IFN-alpha treatment for chronic HCV in a repeat allograft recipient on hemodialysis: a case report.

Interferon alpha (IFN-alpha) can be effective therapy for patients with chronic kidney disease who have chronic hepatitis C (HCV). However, acute allograft rejection has been reported in association with IFN-alpha following kidney transplantation, and therefore IFN therapy is recommended prior to, rather than after, kidney transplantation whenever feasible. The special case of repeat allograft recipients who contract HCV after the first transplantation presents special difficulties. This report features the case of a repeat allograft recipient who presented with neutropenic fevers after 5 months of pegylated IFN-alpha therapy, initiated 6 months following the functional loss of his third graft and the reinitiation of hemodialysis (HD). Physical exam, radiographic and laboratory findings led to allograft nephrectomy. The pathologic findings supported a diagnosis of acute-on-chronic rejection. This represents a rare case of IFN-alpha induced rejection following allograft failure and return to HD in a repeat allograft recipient. It also calls attention to the need for a high index of suspicion for the development of allograft rejection, which may require allograft nephrectomy even after allograft 'failure'.

Analyzing process variation in chart review using a networked spreadsheet application in the Walter Reed Army Medical Center Nephrology Clinic.

The role of reviewer variation in interpreting outcomes of outpatient clinic chart reviews has been poorly studied. The present study used results collected from a network-based spreadsheet application (Microsoft Excel), which is widely available throughout the Army Medical Department, for chart reviews. Data were collected from January 1998 to August 2000, and 2,308 charts of 1,127 patients were reviewed. Results showed a significant improvement in documentation of contact with the referring provider from 1998 to 2000 (55.9% in 1998, 81.6% in 1999, and 80.6% in 2000; p < 0.01 by chi 2 for both). The percentage of charts for new consultations with inadequately controlled blood pressure managed appropriately improved from 73.7% in 1999 to 89.2% in 2000 (p < 0.01 by chi 2). These results persisted in logistic regression analysis controlling for different reviewers. In conclusion, widely available office automation tools allow the systematic analysis of chart review data with the potential to improve practice patterns.

Review of thrombotic thrombocytopenic purpura in the setting of systemic lupus erythematosus.

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) has been described in association with systemic lupus erythematosus (SLE) rarely. The diagnosis of TTP as a process separate from SLE may be difficult because both share similar features, including thrombotic microangiopathy. METHODS: A case is described of the simultaneous occurrence of TTP and SLE. The clinical, laboratory, and histologic findings of the patient are reported. The association of TTP and SLE in the literature is analyzed. We review separately the pathogenesis, role of antiphospholipid antibodies, and the differential diagnosis of TTP complicating the course of SLE. RESULTS: Forty cases of TTP in association with SLE are reported in the world literature. Three distinct groups were defined by the presentation of TTP that occurred subsequent to, before, or simultaneous with SLE (groups 1, 2, and 3, respectively). Renal biopsy in a patient with lupus nephritis may reveal thrombotic microangiopathy, which may be seen independently or represent a concomitant systemic thrombotic process such as TTP, disseminated intravascular coagulation, or antiphospholipid antibody syndrome. CONCLUSION: TTP in association with SLE is rare, and the diagnosis may be challenging. Although the etiology of TTP remains elusive, certain autoimmune mechanisms, platelet abnormalities, and fibrinolytic disorders may be shared with SLE and provide the basis for their association. Management requires timely diagnosis and aggressive treatment by therapeutic plasma exchange.

Effect of glycine on cisplatin nephrotoxicity and heat-shock protein 70 expression in the rat kidney.

Glycine has been shown to protect against cisplatin (CP) nephrotoxicity in rats and to enhance the in vitro expression of heat-shock protein (hsp) 70 in renal epithelial cells following sublethal heat shock. We hypothesized that the protective effect of glycine against CP nephrotoxicity may be due to an up-regulation of Hsp 70 protein expression. Male Sprague-Dawley rats were divided into 4 treatment groups based upon infusion of glycine and injection of CP or their respective vehicles. At 5 days after treatment animals administered CP alone demonstrated a significant decrease in creatinine clearance compared to baseline (0.77 +/- 0.32 mL/min vs. 3.90 +/- 0.87 mL/min, p < 0.05). Treatment with glycine and CP attenuated this response, with no significant decline seen in creatinine clearance at day 5 compared to baseline (2.25 +/- 0.31 mL/min vs. 3.40 +/- 0.86 mL/min). Semiquantitative histological study revealed a marked decrease in proximal tubular injury at the juxtamedullary and outer medullary regions among animals treated with glycine and CP compared to those animals treated with CP alone. There were no differences in renal cortical and medullary Hsp 70 levels by Western immunoblotting between animals treated with glycine and CP compared to CP alone at 4 h and 5 days after treatment. Immunohistochemical studies of animals treated with CP alone revealed the diffuse presence of Hsp 70 in the cytoplasm of injured and necrotic proximal tubular cells 5 days after treatment. Animals receiving CP and glycine demonstrated a more focal presence of Hsp 70 restricted to injured proximal tubular cells, with no staining of uninjured cells. The protective effect of glycine in CP-induced acute and renal failure in the rat does not appear to be associated with enhancement of Hsp 70 expression.

Distribution of the cellular uptake of phosphorothioate oligodeoxynucleotides in the rat kidney in vivo.

Previous animal studies have demonstrated that following systemic administration phosphorothioate oligodeoxynucleotides (S-ODNs) are primarily excreted by the kidneys and that renal tissue levels of S-ODNs exceed that of other organs. Thus, the kidney may be an ideal target organ for application of antisense S-ODNs in vivo. We examined which cells within the rat kidney have uptake of radiolabeled S-ODNs following intravenous infusion. A 20-base 35S-ODN was infused into 6 adult male Wistar rats. Three animals each were sacrificed 30 min and 4 h after infusion. The kidneys were then removed, fixed, and tissue autoradiography was performed. Similar results were obtained in both groups. The highest level of radioactivity was seen within the proximal tubules. Lower levels of activity were seen within the glomerulus, the parietal epithelial cells of Bowman's space, and distal tubular cells. Very weak activity was also detected within the cells of the loop of Henle and the medullary collecting ducts. These results demonstrated that within the kidney S-ODNs were taken up primarily by proximal tubular cells, with much lower uptake by cells in other segments of the nephron.

Sublethal heat shock and cyclosporine exposure produce tolerance against subsequent cyclosporine toxicity.

Sublethal heat shock has been shown to produce tolerance in cells and tissues subsequently exposed to heat or ischemia/ATP depletion. We tested whether heating LLC-PK1 cells for 2 h at 42 degrees C induced heat shock protein-70 (HSP-70) gene expression and conferred tolerance against subsequent cyclosporine A (CyA) toxicity. HSP-70 mRNA was increased immediately after heat shock, returning to baseline by 4 h. HSP-70 protein increased by 1 h after heat shock and declined thereafter, approaching baseline after 72 h. Cells heat shocked at 4 and 24 h prior to CyA exposure were significantly more viable than controls, at CyA concentrations near the median lethal dose (LD50). Cytoprotection declined with time after heat shock, concurrent with declining HSP-70 protein levels. Sublethal CyA exposure (50 micrograms/ml) for 24 h produced upregulation of HSP-70 mRNA and protein. Pretreatment with 50 micrograms/ml CyA for 24 h followed by exposure to a toxic concentration of CyA (200 micrograms/ml) produced significant cytoprotection compared with untreated controls. In conclusion, HSP-70 protein induction by sublethal heat shock or CyA exposure was associated with tolerance against subsequent lethal CyA exposure.