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An unusual presentation of hematuria
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http://www.kidney-international.org & 2011 International Society of Nephrology Kidney International (2011) 79, 923; doi:10.1038/ki.2010.547
An unusual presentation of hematuria Fuad R. Said1, Rogers C. Griffith2 and George P. Bayliss3 1
Department of Medicine, Milford Regional Medical Center, Milford, Massachusetts, USA; 2Department of Pathology, Rhode Island and the Miriam Hospitals, Providence, Rhode Island, USA and 3Division of Kidney Diseases and Hypertension, Department of Medicine, Rhode Island and the Miriam Hospitals, Providence, Rhode Island, USA Correspondence: George P. Bayliss, Division of Kidney Diseases and Hypertension, Department of Medicine, Rhode Island and the Miriam Hospitals, Providence, Rhode Island, USA. E-mail: [email protected]
Figure 1 | Urine and lymphoid tissue from an 83-year-old man with a history of prostate cancer who presented with hematuria. (a) Urine sediment showing red blood cells in rouleaux formation ( 40). (b) Retroperitoneal lymph node biopsy showing infiltrate of large undifferentiated epithelioid cells with focal pleomorphic features, consistent with non-small cell carcinoma ( 400).
An 83-year-old man with a past medical history of prostate cancer presented after he developed hematuria. Serum creatinine was 1.3 mg/dl. Serum albumin was 1.4 mg/dl. Urine albumin/creatinine ratio was 1.6 g/g; protein/creatinine ratio was 7 g/g. Corrected serum/calcium was 11.9 mg/dl. Computed tomography of the abdomen and pelvis showed retroperitoneal lymphadenopathy. Urine sediment showed red blood cells in rouleaux formation (Figure 1a). Urine protein electrophoresis showed a paraprotein band, and urine immunofixation electrophoresis showed a kappa free lightchain band in the beta region. Biopsy of a retroperitoneal lymph node revealed non-small-cell carcinoma of uncertain origin (Figure 1b). Rouleaux formation of red blood cells in the patient’s urine is an effect of paraproteins on the negative surface charge of red blood cells and underscores the need to look for underlying malignancy in any patient with new-onset nephrotic-range proteinuria. The phenomenon of rouleaux formation in plasma is well known, but there is little literature on rouleaux in urine. The repulsive forces that prevent red blood cells from aggregating arise from negatively charged sialic acid residues on red blood cell membranes, described as the zeta potential. The zeta
Kidney International (2011) 79, 923
potential is attenuated by ions in the surrounding medium and is modified by the dielectric effect of proteins, particularly asymmetrical paraproteins, which exert a disproportionately large effect because they are oriented by the electrical field.1 In serum, rouleaux formation is noted in paraproteinemias like Waldenstrom’s macroglobulinemia and multiple myeloma: the large paraproteins are positively charged at physiological pH and bind to red blood cells, leading to hyperviscosity.2 Experimentally, divalent cations further reduce the zeta potential and increase red blood cell aggregation.3 We surmise that nephrotic-range proteinuria was the result of the underlying malignancy, a non-small-cell carcinoma of unclear origin. The most common forms of tumor associated with nephropathy are solid ones, particularly adenocarcinoma of the lung and gastrointestinal tract.4 1. 2. 3. 4.
Bull SB, Brailsford JD. The zeta sedimentation rate. Blood 1972; 40: 350–359. Buxbaum J. Hyperviscosity syndrome in dysproteinemias. Am J Med Sci 1972; 264: 123–126. Jan KM, Chien S. Influence of the ionic composition of fluid medium on red cell aggregation. J Gen Physiol 1972; 61: 655–668. Davison AM. Renal diseases associated with malignancy. Nephrol Dial Transplant 2001; 16(Suppl 6): 13–14.
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http://www.kidney-international.org & 2011 International Society of Nephrology Kidney International (2011) 79, 923; doi:10.1038/ki.2010.547
An unusual presentation of hematuria Fuad R. Said1, Rogers C. Griffith2 and George P. Bayliss3 1
Department of Medicine, Milford Regional Medical Center, Milford, Massachusetts, USA; 2Department of Pathology, Rhode Island and the Miriam Hospitals, Providence, Rhode Island, USA and 3Division of Kidney Diseases and Hypertension, Department of Medicine, Rhode Island and the Miriam Hospitals, Providence, Rhode Island, USA Correspondence: George P. Bayliss, Division of Kidney Diseases and Hypertension, Department of Medicine, Rhode Island and the Miriam Hospitals, Providence, Rhode Island, USA. E-mail: [email protected]
Figure 1 | Urine and lymphoid tissue from an 83-year-old man with a history of prostate cancer who presented with hematuria. (a) Urine sediment showing red blood cells in rouleaux formation ( 40). (b) Retroperitoneal lymph node biopsy showing infiltrate of large undifferentiated epithelioid cells with focal pleomorphic features, consistent with non-small cell carcinoma ( 400).
An 83-year-old man with a past medical history of prostate cancer presented after he developed hematuria. Serum creatinine was 1.3 mg/dl. Serum albumin was 1.4 mg/dl. Urine albumin/creatinine ratio was 1.6 g/g; protein/creatinine ratio was 7 g/g. Corrected serum/calcium was 11.9 mg/dl. Computed tomography of the abdomen and pelvis showed retroperitoneal lymphadenopathy. Urine sediment showed red blood cells in rouleaux formation (Figure 1a). Urine protein electrophoresis showed a paraprotein band, and urine immunofixation electrophoresis showed a kappa free lightchain band in the beta region. Biopsy of a retroperitoneal lymph node revealed non-small-cell carcinoma of uncertain origin (Figure 1b). Rouleaux formation of red blood cells in the patient’s urine is an effect of paraproteins on the negative surface charge of red blood cells and underscores the need to look for underlying malignancy in any patient with new-onset nephrotic-range proteinuria. The phenomenon of rouleaux formation in plasma is well known, but there is little literature on rouleaux in urine. The repulsive forces that prevent red blood cells from aggregating arise from negatively charged sialic acid residues on red blood cell membranes, described as the zeta potential. The zeta
Kidney International (2011) 79, 923
potential is attenuated by ions in the surrounding medium and is modified by the dielectric effect of proteins, particularly asymmetrical paraproteins, which exert a disproportionately large effect because they are oriented by the electrical field.1 In serum, rouleaux formation is noted in paraproteinemias like Waldenstrom’s macroglobulinemia and multiple myeloma: the large paraproteins are positively charged at physiological pH and bind to red blood cells, leading to hyperviscosity.2 Experimentally, divalent cations further reduce the zeta potential and increase red blood cell aggregation.3 We surmise that nephrotic-range proteinuria was the result of the underlying malignancy, a non-small-cell carcinoma of unclear origin. The most common forms of tumor associated with nephropathy are solid ones, particularly adenocarcinoma of the lung and gastrointestinal tract.4 1. 2. 3. 4.
Bull SB, Brailsford JD. The zeta sedimentation rate. Blood 1972; 40: 350–359. Buxbaum J. Hyperviscosity syndrome in dysproteinemias. Am J Med Sci 1972; 264: 123–126. Jan KM, Chien S. Influence of the ionic composition of fluid medium on red cell aggregation. J Gen Physiol 1972; 61: 655–668. Davison AM. Renal diseases associated with malignancy. Nephrol Dial Transplant 2001; 16(Suppl 6): 13–14.
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