- Email: [email protected]
Are podocytes in the urine of preterm infants a marker of drug induced glomerular injury?
S74
PATHOLOGY 2012 ABSTRACT SUPPLEMENT
MODULATION OF AQUAPORIN 1 FUNCTION ALTERS PROLIFERATION OF MALIGNANT MESOTHELIAL CELLS Joanna Czerwinski1, Kim M. Griggs1, Douglas W. Henderson1,2, Andrea J. Yool3, Sonja Klebe1,2 1 Department of Anatomical Pathology, Flinders University, Bedford Park, 2SA Pathology, Flinders Medical Centre, Bedford Park, and 3Department of Physiology, Adelaide University, Adelaide, SA, Australia Background: Malignant mesothelioma (MM) is an aggressive tumour of serosal membranes with a poor prognosis. We have identified aquaporin 1 (AQP1) as a significant prognostic marker. Aims: To investigate if expression levels of AQP1 correlate with proliferation of MM cells and if alteration of AQP1 function by pharmacological blockers and siRNA cell inhibits cell proliferation in vitro. Methods: MM cell lines (H28, H2052, 211H, H226 and H2452) and normal mesothelial cells (MET5A) obtained from the ATCC and primary MM cells harvested from malignant pleural effusions were used. AQP1 expression was determined by immunohistochemistry (IHC) and mesothelial phenotype confirmed. Cell proliferation was measured with and without altered AQP1 channel function using the MTS assay. Results: AQP1-positive cell lines (H226 and H28) and patientderived MM cells with high AQP1 expression had overall higher proliferation rates than the AQP1 negative cells (H2052, 211H, H2452 and Met5A). AQP1 modulation by pharmacological agents from a custom synthetic chemical library can decrease cell proliferation without inducing cytotoxicity or increasing apoptosis. Conclusions: AQP1 is a prognostic marker for MM and modulation of AQP1 function can alter MM cell proliferation. This has treatment potential. AQP1 inhibition by siRNA will further clarify the molecular mechanism leading to specific AQP1 modulation. ARE PODOCYTES IN THE URINE OF PRETERM INFANTS A MARKER OF DRUG INDUCED GLOMERULAR INJURY? A. L. Kent1,2, L. Brown3, M. Broom1, A. Broomfield3, J. E. Dahlstrom2,3 1 Department of Neonatology, Canberra Hospital, Woden, 2 Australian National University Medical School, Canberra, and 3 Department of Anatomical Pathology, Canberra Hospital, Woden, ACT, Australia Preterm infants are delivered while glomerulogenesis is ongoing and thus may be exposed to a number of insults including medications that may affect renal development. Podocytes detected in the urine are an indicator of glomerular injury in a number of renal conditions. Aims: To determine whether preterm and term infants excrete podocytes in their urine and if exposure to gentamicin and indomethacin increased podocyte excretion in their urine. Methods: Preterm infants less than 33 weeks gestation had urine collected each day while receiving either gentamicin or indomethacin and the number of casts and podocytes present in the urine were compared with preterm and term control infants urine who did not receive gentamicin or indomethacin. Results and conclusions: Forty-two neonates were included in the study. Podocytes were present in small numbers (<2) in the urine of both preterm and term control neonates. There were increased numbers of podocytes in the urine of preterm neonates receiving
Pathology (2012), 44(S1)
indomethacin ( p ¼ 0.02). The increased number of podocytes in preterm neonates receiving indomethacin suggests that glomerular injury is occurring. It is unknown whether injury to glomeruli during glomerulogenesis in preterm neonates has long-term sequelae for renal development and function into adulthood. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS TYPE III, STRIFE VARIANT Dariush Daneshvar1, Jeanne Tomlinson1, Ross Boadle2 1 Department of Tissue Pathology and Diagnostic Oncology, and 2 Electron Microscopy Unit, Institute of Clinical Pathology and Medical Research, Westmead Hospital, NSW, Australia Membranoproliferative glomerulonephritis (MPGN) type III, Strife variant is very rare. Although the actual incidence of this variant is unclear, it is thought to account for less than 1% of glomerulonephritis diagnoses. It commonly affects young people, who usually present with nephrotic syndrome. There are some recognised secondary associations, namely Sjo¨gren syndrome, cirrhosis, human immunodeficiency virus infection, and systemic lupus erythematosus. Here, we report a case of membranoproliferative glomerulonephritis, Strife variant. The light microscopic, immunofluorescence and electron microscopic findings that facilitate its diagnosis will be presented and discussed. References 1. Mathieson PW. Mesangiocapillary glomerulonephritis. In: Pusey CD, editor. The Treatment of Glomerulonephritis. Boston: Kluwer Academic Publishers, 1999; 81–92. 2. Strife CF, McEnery PT, McAdams AJ, West CD. Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane. Clin Nephrol 1977; 7: 65–72.
INTRAVASCULAR RENAL HAEMANGIOMA RESEMBLING THE RED PULP OF SPLEEN ARISING FROM WITHIN THE RENAL VEIN: A CASE REPORT Dariush Daneshvar, Shaun Chou, Jeanne Tomlinson, Anita Achan, Winny Varikatt, Raghwa Sharma Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia Vascular tumours are very uncommon in the kidney and most of these have been described in single case reports. Some of these can be diagnosed radiologically so the histological features of many of these tumours are not well recognised. We report a case of a haemangioma arising from within the renal vein in a patient with chronic renal failure and bilateral adrenal cortical hyperplasia. The tumour has an unusual sinusoidal architecture and focal extramedullary haematopoiesis reminiscent of the spleen. As expected, the endothelial cells stain positively for CD31 and CD34 but negative for CD8. We will also briefly discuss the clinical and histological features of this unusual tumour based on literature reviews. References 1. Brown JG, Folpe AL, Rao P, et al. Primary vascular tumors and tumor-like lesions of the kidney: a clinicopathologic analysis of 25 cases. Am J Surg Pathol 2010; 34: 942–9. 2. Montgomery E, Epstein JI. Anastomosing hemangioma of the genitourinary tract: a previously undescribed lesion mimicking angiosarcoma. Mod Pathol 2009; 22: 184–5A. 3. Zhao X, Zhang J, Zhong Z, et al. Large renal cavernous hemangioma with renal vein thrombosis: case report and review of literature. Urology 2009; 73: e441–3.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited. Copyright
PATHOLOGY 2012 ABSTRACT SUPPLEMENT
MODULATION OF AQUAPORIN 1 FUNCTION ALTERS PROLIFERATION OF MALIGNANT MESOTHELIAL CELLS Joanna Czerwinski1, Kim M. Griggs1, Douglas W. Henderson1,2, Andrea J. Yool3, Sonja Klebe1,2 1 Department of Anatomical Pathology, Flinders University, Bedford Park, 2SA Pathology, Flinders Medical Centre, Bedford Park, and 3Department of Physiology, Adelaide University, Adelaide, SA, Australia Background: Malignant mesothelioma (MM) is an aggressive tumour of serosal membranes with a poor prognosis. We have identified aquaporin 1 (AQP1) as a significant prognostic marker. Aims: To investigate if expression levels of AQP1 correlate with proliferation of MM cells and if alteration of AQP1 function by pharmacological blockers and siRNA cell inhibits cell proliferation in vitro. Methods: MM cell lines (H28, H2052, 211H, H226 and H2452) and normal mesothelial cells (MET5A) obtained from the ATCC and primary MM cells harvested from malignant pleural effusions were used. AQP1 expression was determined by immunohistochemistry (IHC) and mesothelial phenotype confirmed. Cell proliferation was measured with and without altered AQP1 channel function using the MTS assay. Results: AQP1-positive cell lines (H226 and H28) and patientderived MM cells with high AQP1 expression had overall higher proliferation rates than the AQP1 negative cells (H2052, 211H, H2452 and Met5A). AQP1 modulation by pharmacological agents from a custom synthetic chemical library can decrease cell proliferation without inducing cytotoxicity or increasing apoptosis. Conclusions: AQP1 is a prognostic marker for MM and modulation of AQP1 function can alter MM cell proliferation. This has treatment potential. AQP1 inhibition by siRNA will further clarify the molecular mechanism leading to specific AQP1 modulation. ARE PODOCYTES IN THE URINE OF PRETERM INFANTS A MARKER OF DRUG INDUCED GLOMERULAR INJURY? A. L. Kent1,2, L. Brown3, M. Broom1, A. Broomfield3, J. E. Dahlstrom2,3 1 Department of Neonatology, Canberra Hospital, Woden, 2 Australian National University Medical School, Canberra, and 3 Department of Anatomical Pathology, Canberra Hospital, Woden, ACT, Australia Preterm infants are delivered while glomerulogenesis is ongoing and thus may be exposed to a number of insults including medications that may affect renal development. Podocytes detected in the urine are an indicator of glomerular injury in a number of renal conditions. Aims: To determine whether preterm and term infants excrete podocytes in their urine and if exposure to gentamicin and indomethacin increased podocyte excretion in their urine. Methods: Preterm infants less than 33 weeks gestation had urine collected each day while receiving either gentamicin or indomethacin and the number of casts and podocytes present in the urine were compared with preterm and term control infants urine who did not receive gentamicin or indomethacin. Results and conclusions: Forty-two neonates were included in the study. Podocytes were present in small numbers (<2) in the urine of both preterm and term control neonates. There were increased numbers of podocytes in the urine of preterm neonates receiving
Pathology (2012), 44(S1)
indomethacin ( p ¼ 0.02). The increased number of podocytes in preterm neonates receiving indomethacin suggests that glomerular injury is occurring. It is unknown whether injury to glomeruli during glomerulogenesis in preterm neonates has long-term sequelae for renal development and function into adulthood. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS TYPE III, STRIFE VARIANT Dariush Daneshvar1, Jeanne Tomlinson1, Ross Boadle2 1 Department of Tissue Pathology and Diagnostic Oncology, and 2 Electron Microscopy Unit, Institute of Clinical Pathology and Medical Research, Westmead Hospital, NSW, Australia Membranoproliferative glomerulonephritis (MPGN) type III, Strife variant is very rare. Although the actual incidence of this variant is unclear, it is thought to account for less than 1% of glomerulonephritis diagnoses. It commonly affects young people, who usually present with nephrotic syndrome. There are some recognised secondary associations, namely Sjo¨gren syndrome, cirrhosis, human immunodeficiency virus infection, and systemic lupus erythematosus. Here, we report a case of membranoproliferative glomerulonephritis, Strife variant. The light microscopic, immunofluorescence and electron microscopic findings that facilitate its diagnosis will be presented and discussed. References 1. Mathieson PW. Mesangiocapillary glomerulonephritis. In: Pusey CD, editor. The Treatment of Glomerulonephritis. Boston: Kluwer Academic Publishers, 1999; 81–92. 2. Strife CF, McEnery PT, McAdams AJ, West CD. Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane. Clin Nephrol 1977; 7: 65–72.
INTRAVASCULAR RENAL HAEMANGIOMA RESEMBLING THE RED PULP OF SPLEEN ARISING FROM WITHIN THE RENAL VEIN: A CASE REPORT Dariush Daneshvar, Shaun Chou, Jeanne Tomlinson, Anita Achan, Winny Varikatt, Raghwa Sharma Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia Vascular tumours are very uncommon in the kidney and most of these have been described in single case reports. Some of these can be diagnosed radiologically so the histological features of many of these tumours are not well recognised. We report a case of a haemangioma arising from within the renal vein in a patient with chronic renal failure and bilateral adrenal cortical hyperplasia. The tumour has an unusual sinusoidal architecture and focal extramedullary haematopoiesis reminiscent of the spleen. As expected, the endothelial cells stain positively for CD31 and CD34 but negative for CD8. We will also briefly discuss the clinical and histological features of this unusual tumour based on literature reviews. References 1. Brown JG, Folpe AL, Rao P, et al. Primary vascular tumors and tumor-like lesions of the kidney: a clinicopathologic analysis of 25 cases. Am J Surg Pathol 2010; 34: 942–9. 2. Montgomery E, Epstein JI. Anastomosing hemangioma of the genitourinary tract: a previously undescribed lesion mimicking angiosarcoma. Mod Pathol 2009; 22: 184–5A. 3. Zhao X, Zhang J, Zhong Z, et al. Large renal cavernous hemangioma with renal vein thrombosis: case report and review of literature. Urology 2009; 73: e441–3.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited. Copyright