CXCL10 and CXCL13 Expression were highly up-regulated in peripheral blood mononuclear cells in acute rejection and poor response to anti-rejection therapy.

BACKGROUND: Acute rejection is still one of the main complications which enhances the cost and the risk to renal graft failure. Chemokines, interacting with respective receptors, can recruit leukocytes into grafts and mediate allograft rejection. In this study, we aimed to analyze gene expression of chemokines including CCL5/RANTES, CXCL10/IP-10, CXCL13/BCA-1, and receptors of CCR5, CXCR3, CXCR5 in peripheral blood mononuclear cells (PBMCs) during acute renal allograft rejection METHODS: Gene expression of all these chemokines and receptors in PBMCs were analyzed by real-time PCR from 14 stable recipients, 32 biopsy-proven acute rejection (AR), and 5 acute tubular necrosis (ATN). RESULTS: Gene expression of CCL5, CXCL10, CXCL13, and CCR5 were up-regulated both in AR and ATN group compared to stable recipients (fold change>2, P<0.05). Serum creatinine recovered to baseline level after anti-rejection therapy was defined as AR-sensitive and creatinine maintained above 200 µmol/L as AR-resistant. Expression of CXCL10 and CXCL13 were 5.98-, 2.94-, and 20.5, 10.8-fold change in AR-resistant and AR-sensitive compared to stable recipients, respectively. The expression of CXCL10 and CXCL13 was a twofold change in AR-resistant compared to AR-sensitive recipients (P<0.05). Five out of ten AR-resistant recipients lost graft function in the follow-up. CONCLUSION: CXCL10 and CXCL13 expression were highly up-regulated in PBMCs in acute renal allograft rejection, especially in poor response to anti-rejection therapy and detrimental prognosis.

Early critical cortical infarction by anti-angiotensin II type 1 receptor antibody: A case report and literature review.

RATIONALE: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been demonstrated to increase the risk of antibody-mediated rejection. We report a case of AT1R-Ab mediated rejection which caused early critical cortical infarction. PATIENT CONCERNS: A 52-year-old man with end-stage kidney disease underwent preemptive kidney transplantation (KT) from his wife. He had no immunologic risk except ABO incompatibility. Proper desensitization treatment were applied prior to KT. On postoperative day 1, he showed stable clinical course with adequate urine output, but there was no decrease in serum creatinine level and imaging studies showed hypoperfusion in the transplanted kidney. DIAGNOSES: Allograft biopsy revealed total cortical infarction with severe necrotizing vasculitis, but the medullary area was preserved. Serum AT1R-Ab concentration was elevated from 10.9 U/mL before KT to 19.1 U/mL on 7 days after KT. INTERVENTIONS: He was treated with plasmapheresis, intravenous immunoglobulin, rituximab, high-dose methylprednisolone, and bortezomib. OUTCOMES: The treatment showed a partial response, and he was discharged with 7.3 mg/dL creatinine level. At 4 months, his creatinine plateaued at 5.5 mg/dL and AT1R-Ab decreased to 3.6 U/mL. LESSONS: This case highlights the risk of early active antibody-mediated rejection by preformed AT1R-Ab, suggesting its ability to exhibit atypical histopathologic findings, such as total cortical infarction.

Spirulina platensis protects against renal injury in rats with gentamicin-induced acute tubular necrosis.

The present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80 mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80 mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties.

Renal cortical necrosis related to paraneoplastic antiphospholipid syndrome.

Acute bilateral renal cortical necrosis is a very rare cause of acute renal failure. We report here for the first time a case related to antiphospholipid syndrome, paraneoplastic of a lung neoplasia. A 46-year-old male smoker without medical history was admitted for acute dyspnea and anuria. Biological examination showed acute renal failure associated with hyperkalemia, high serum lactate dehydrogenase level, and prolonged activated thrombin time (ratio 1.29). Chest radiograph showed a right laterotracheal round lesion. A percutaneous left renal biopsy showed cortical necrosis, and renal arteriography confirmed bilateral cortical necrosis. Blood examination showed antiphospholipid antibodies type anticardiolipin. Chest computed tomographic scan confirmed the presence of a lung tumor. Two years after tumor surgery, the patient was still anuric and on long-term hemodialysis therapy, but antiphospholipid antibody results were negative. This case describes the first association of antiphospholipid syndrome to epidermoid lung cancer, shown by cortical bilateral necrosis. It also emphasizes the utility of renal biopsy in case of an unusual acute renal failure.

Acute renal cortical necrosis. Variable course and changing prognosis.

Three cases of acute bilateral renal cortical necrosis, each with a different clinical course, are discussed. One patient spontaneously recovered renal function after prolonged oliguria. This case should be added to the small number of similar case reports in the literature. The second patient recovered adequate renal function temporarily, but eventually required chronic hemodialysis and renal transplantation. There was pathological evidence of progression from focal to massive cortical necrosis. The third patient never regained renal function, but is well after dialysis and transplantation. The influence of modern theories of pathogenesis of the disease, and increased availability of dialysis, are discussed in relation to the initial prognostic assessment of the patient with cortical necrosis.

Erythropoietin deficiency in acute crescentic glomerulonephritis and in total bilateral renal cortical necrosis.

Six patients with acute renal failure, in five cases due to acute crescentic glomerulonephritis and in one case due to total bilateral renal cortical necrosis, were studied. All had serum erythropoietin (EPO) concentrations in the normal range, despite a relatively severe anaemia. Half-life and plasma clearance of intravenously injected recombinant human erythropoietin (rhEPO) were determined. The results indicate that the lack of compensatory increase in serum EPO to the anaemic stimulus is not due to increased catabolism, but to decreased synthesis of the renal hormone. Two patients were treated with rhEPO (Eprex). In marked contrast to untreated controls, both patients responded with vigorous reticulocytosis and normalization of haemoglobin levels while they were still in severe renal failure. These results are similar to our previous findings in patients with acute renal failure due to tubular necrosis. Under all three conditions the defective EPO synthesis is probably the dominant pathogenetic factor for the largely aregeneratory anaemia of prolonged cases, and for the sluggish restoration of red cell mass during recovery of renal function. It is concluded that defective synthesis of EPO is not only a permanent and irreversible feature of severe chronic renal failure, but that it is also present, usually in a transient and reversible form, in different types of acute renal failure.

Hypertension in end-stage renal disease. The relationship between blood pressure, plasma renin, plasma renin substrate and exchangeable sodium in chronic hemodialysis patients.

Blood pressure (BP), plasma renin concentration (PRC), plasma renin substrate concentration (PRSC) and exchangeable sodium (ES) have been studied in 27 patients undergoing regular hemodialysis because of end-stage renal disease. PRC was significantly higher in the hypertensive than in the normotensive patients. The pattern of PRSC was similar in the groups of patients but with a marked individual variation. ES was slightly lower in the hypertensives than in the normotensives but the difference was not statistically significant. Multiple regression analysis demonstrated a significant correlation between mean BP, the natural logarithm of PRC and ES, but the effect of ES was negligible. PRC was negatively correlated to ES in all patients, including the hypertensives. These results strongly suggest that the renin-angiotensin system is the most important factor involved in the pathogenesis of hypertension in end-stage renal disease, when sodium balance is adequately controlled. A clinical application of the predictive value of PRC concerning the effect of bilateral nephrectomy on hypertension is outlined.