letter to the editor
http://www.kidney-international.org & 2014 International Society of Nephrology
Utility of renal biopsy in the clinical management of renal disease: hematuria should not be missed To the Editor: In a recent issue, Dhaun et al.1 reviewed the utility of renal biopsy in the clinical management of renal disease. The article describes standard and expanded indications for renal biopsy, such as renal biopsy in the elderly, in those with diabetes or ‘hypertensive nephropathy’ and even renal biopsy in advanced chronic kidney disease (CKD). However, the isolated hematuria should also not be missed. Typically, nephrologists tend to diagnose, monitor, and treat another fundamental manifestation of glomerular injury, proteinuria. Persistent glomerular hematuria is very common in daily clinical practice and is typically due to thin basement membrane nephropathy (TBMN) or less often from Alport syndrome (AS).2 AS and TBMN may be clinically indistinguishable. The differentiation is, however, of great importance due to different risks of CKD for the individual and their family members. A group of European, American, and Australian experts in their recent guidelines recommend renal biopsy in suspected AS for glomerular basement membrane (GBM) ‘ultrastructure, collagen IV composition, and an assessment of damage’.3 The tissue distribution and trimer composition of the different collagen IV molecules are well known. The diagnosis of AS is highly likely if GBM lacks the collagen IV a5 chain, and in most cases, immunohistochemical staining for the alpha-3 and alpha-5 chains will be pathognomonic. The same guidelines state that ‘individuals suspected of having TBMN should undergo renal biopsy if they have atypical features y or if X-linked Alport syndrome y cannot be excluded’.3 Renal biopsy can reveal important findings even in ‘loin pain–hematuria syndrome’, where thick or thin GBMs have been observed.4 Therefore, renal biopsy ‘forms an invaluable part of the diagnostic process’ in hematuric syndromes as well.
The Authors Reply: We thank Dr Miglinas for his letter1 and agree that renal biopsy may be helpful in clarifying between a diagnosis of thin basement membrane nephropathy (TBMN) and Alport’s syndrome (AS), which may be clinically indistinguishable. The importance in discriminating between them relates to their differing risks of chronic kidney disease and implications for family members. Both TBMN and AS typically present in childhood with persistent microhematuria alongside preserved renal function. Both conditions are a consequence of mutations in collagen type IV. Light microscopy and standard immunofluorescence are often normal and hence discriminating between the two using renal biopsy requires assessment of ultrastructure, which may not be available in some centers. In TBMN, electron microscopy reveals isolated widespread thinning of the glomerular basement membrane (GBM; o250 nm in adults).2 In established AS, there is classic thickening and lamellation of the GBM. Importantly, from a diagnostic perspective, in the early clinical course of AS the ultrastructural appearances may be indistinguishable from those of TBMN.3 The use of commercially available antibodies against the different subunits of collagen IV may aid in the diagnosis and prognosis of AS, as well as in differentiating it from TBMN (which retains a normal staining distribution for all collagen IV subunits). However, across the world, there is limited experience in using these antibodies, and some patients with AS may retain a normal staining pattern.4 Finally, in loin pain–hematuria syndrome renal biopsy may reveal a cause for the symptoms—IgA nephropathy, vasculitis—or otherwise, as suggested, reveal varying thickness of the GBM. 1. 2. 3.
4. 1. 2. 3.
Dhaun N, Bellamy CO, Cattran DC et al. Utility of renal biopsy in the clinical management of renal disease. Kidney Int 2014; 85: 1039–1048. Moreno JA, Martı´n-Cleary C, Gutie´rrez E et al. Haematuria: the forgotten CKD factor? Nephrol Dial Transplant 2012; 27: 28–34. Savige J, Gregory M, Gross O et al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol 2013; 24: 364–375. Spetie DN, Nadasdy T, Nadasdy G et al. Proposed pathogenesis of idiopathic loin pain–hematuria syndrome. Am J Kidney Dis 2006; 47: 419–427.
Miglinas M. Utility of renal biopsy in the clinical magement of renal disease: hematuria should not be missed. Kidney Int 2014; 86: 1269. Tryggvason K, Patrakka J. Thin basement membrane nephropathy. J Am Soc Nephrol 2006; 17: 813–822. Rumpelt HJ. Hereditary nephropathy (Alport syndrome): correlation of clinical data with glomerular basement membrane alterations. Clin Nephrol 1980; 13: 203–207. Kashtan CE, Segal Y. Genetic disorders of glomerular basement membranes. Nephron Clin Pract 2011; 118: 9–18.
Neeraj Dhaun1,2, Christopher O. Bellamy3, Daniel C. Cattran4 and David C. Kluth2
1 Nephrology Center, Vilnius University, Vilnius, Lithuania Correspondence: Marius Miglinas, Nephrology Center, Vilnius University, Santariskiu 2, Vilnius LT-08661, Lithuania. E-mail: [email protected]
1 BHF Centre of Research Excellence, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK; 2Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK; 3Department of Pathology, Royal Infirmary of Edinburgh, Edinburgh, UK and 4University Health Network, Toronto, Ontario, Canada Correspondence: Neeraj Dhaun, BHF Centre of Research Excellence, The Queen’s Medical Research Institute, University of Edinburgh, 3rd Floor East, Room E3.23, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. E-mail: [email protected]
Kidney International (2014) 86, 1269; doi:10.1038/ki.2014.277
Kidney International (2014) 86, 1269; doi:10.1038/ki.2014.278
4.
Marius Miglinas1
Kidney International (2014) 86, 1269–1272
1269
http://www.kidney-international.org & 2014 International Society of Nephrology
Utility of renal biopsy in the clinical management of renal disease: hematuria should not be missed To the Editor: In a recent issue, Dhaun et al.1 reviewed the utility of renal biopsy in the clinical management of renal disease. The article describes standard and expanded indications for renal biopsy, such as renal biopsy in the elderly, in those with diabetes or ‘hypertensive nephropathy’ and even renal biopsy in advanced chronic kidney disease (CKD). However, the isolated hematuria should also not be missed. Typically, nephrologists tend to diagnose, monitor, and treat another fundamental manifestation of glomerular injury, proteinuria. Persistent glomerular hematuria is very common in daily clinical practice and is typically due to thin basement membrane nephropathy (TBMN) or less often from Alport syndrome (AS).2 AS and TBMN may be clinically indistinguishable. The differentiation is, however, of great importance due to different risks of CKD for the individual and their family members. A group of European, American, and Australian experts in their recent guidelines recommend renal biopsy in suspected AS for glomerular basement membrane (GBM) ‘ultrastructure, collagen IV composition, and an assessment of damage’.3 The tissue distribution and trimer composition of the different collagen IV molecules are well known. The diagnosis of AS is highly likely if GBM lacks the collagen IV a5 chain, and in most cases, immunohistochemical staining for the alpha-3 and alpha-5 chains will be pathognomonic. The same guidelines state that ‘individuals suspected of having TBMN should undergo renal biopsy if they have atypical features y or if X-linked Alport syndrome y cannot be excluded’.3 Renal biopsy can reveal important findings even in ‘loin pain–hematuria syndrome’, where thick or thin GBMs have been observed.4 Therefore, renal biopsy ‘forms an invaluable part of the diagnostic process’ in hematuric syndromes as well.
The Authors Reply: We thank Dr Miglinas for his letter1 and agree that renal biopsy may be helpful in clarifying between a diagnosis of thin basement membrane nephropathy (TBMN) and Alport’s syndrome (AS), which may be clinically indistinguishable. The importance in discriminating between them relates to their differing risks of chronic kidney disease and implications for family members. Both TBMN and AS typically present in childhood with persistent microhematuria alongside preserved renal function. Both conditions are a consequence of mutations in collagen type IV. Light microscopy and standard immunofluorescence are often normal and hence discriminating between the two using renal biopsy requires assessment of ultrastructure, which may not be available in some centers. In TBMN, electron microscopy reveals isolated widespread thinning of the glomerular basement membrane (GBM; o250 nm in adults).2 In established AS, there is classic thickening and lamellation of the GBM. Importantly, from a diagnostic perspective, in the early clinical course of AS the ultrastructural appearances may be indistinguishable from those of TBMN.3 The use of commercially available antibodies against the different subunits of collagen IV may aid in the diagnosis and prognosis of AS, as well as in differentiating it from TBMN (which retains a normal staining distribution for all collagen IV subunits). However, across the world, there is limited experience in using these antibodies, and some patients with AS may retain a normal staining pattern.4 Finally, in loin pain–hematuria syndrome renal biopsy may reveal a cause for the symptoms—IgA nephropathy, vasculitis—or otherwise, as suggested, reveal varying thickness of the GBM. 1. 2. 3.
4. 1. 2. 3.
Dhaun N, Bellamy CO, Cattran DC et al. Utility of renal biopsy in the clinical management of renal disease. Kidney Int 2014; 85: 1039–1048. Moreno JA, Martı´n-Cleary C, Gutie´rrez E et al. Haematuria: the forgotten CKD factor? Nephrol Dial Transplant 2012; 27: 28–34. Savige J, Gregory M, Gross O et al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol 2013; 24: 364–375. Spetie DN, Nadasdy T, Nadasdy G et al. Proposed pathogenesis of idiopathic loin pain–hematuria syndrome. Am J Kidney Dis 2006; 47: 419–427.
Miglinas M. Utility of renal biopsy in the clinical magement of renal disease: hematuria should not be missed. Kidney Int 2014; 86: 1269. Tryggvason K, Patrakka J. Thin basement membrane nephropathy. J Am Soc Nephrol 2006; 17: 813–822. Rumpelt HJ. Hereditary nephropathy (Alport syndrome): correlation of clinical data with glomerular basement membrane alterations. Clin Nephrol 1980; 13: 203–207. Kashtan CE, Segal Y. Genetic disorders of glomerular basement membranes. Nephron Clin Pract 2011; 118: 9–18.
Neeraj Dhaun1,2, Christopher O. Bellamy3, Daniel C. Cattran4 and David C. Kluth2
1 Nephrology Center, Vilnius University, Vilnius, Lithuania Correspondence: Marius Miglinas, Nephrology Center, Vilnius University, Santariskiu 2, Vilnius LT-08661, Lithuania. E-mail: [email protected]
1 BHF Centre of Research Excellence, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK; 2Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK; 3Department of Pathology, Royal Infirmary of Edinburgh, Edinburgh, UK and 4University Health Network, Toronto, Ontario, Canada Correspondence: Neeraj Dhaun, BHF Centre of Research Excellence, The Queen’s Medical Research Institute, University of Edinburgh, 3rd Floor East, Room E3.23, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. E-mail: [email protected]
Kidney International (2014) 86, 1269; doi:10.1038/ki.2014.277
Kidney International (2014) 86, 1269; doi:10.1038/ki.2014.278
4.
Marius Miglinas1
Kidney International (2014) 86, 1269–1272
1269
