Is there a link between diabetic glomerular injury and crescent formation? A case report and literature review
© Otani et al.; licensee BioMed Central Ltd. 2012
Received: 9 March 2012
Accepted: 14 April 2012
Published: 20 April 2012
Glomerular crescents are most commonly associated with rapidly progressive crescentic glomerulonephritis; however, they also develop in response to a wide range of primary and secondary glomerular injuries. Since various kind of glomerulopathies occasionally overlay diabetic glomerular injuries, the presence of crescents in renal biopsy specimens of diabetics may have stimulated a search for etiologies other than diabetes. In this report, we describe an unusual case of diabetic glomerulosclerosis with peculiar extracapillary proliferation. Although such a relationship has so far been ignored in most of the literature, the etiological linkage between diabetic glomerulosclerosis and the development of crescents may not be exceptional. We have reviewed the previous literature and herein discuss the pathological implications of the development of crescents in patients with diabetic glomerulosclerosis.
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Glomerular crescents, which are formed by the accumulation of cells in Bowman`s space that surround and compress the glomerulus, are most commonly associated with rapidly progressive crescentic glomerulonephritis (RPGN); however, they also develop in response to a wide range of primary and secondary glomerular injuries, including lupus nephritis, purpura nephritis, IgA nephropathy, post-infectious glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN) [1–3]. Not surprisingly, these glomerulopathies occasionally overlay diabetic glomerular injuries [4–7]. Therefore, the presence of crescents in renal biopsy specimens of diabetics may have served to stimulate a search for etiologies other than diabetes . In this report, we describe an unusual case of diabetic glomerulosclerosis with peculiar extracapillary proliferation.
A 53-year-old male was admitted to our hospital in July 2010 with chief complaints of progressive swelling of the legs and shortness of breath. He had gained approximately 25 kg in the past five months. Eleven years prior to admission, he was found to have type 2 diabetes with a fasting blood glucose (FBS) of 200 mg/dl and HbA1c of 8.2, for which he had received sporadic medical care. However, he gradually developed a loss of appetite for psychosomatic reasons, making the use of hyperglycemia controlling agents unnecessary in the beginning of January 2010 (HbA1c 4.9). He neither smoked nor drank alcohol and denied using any drugs. No apparent past history of any renal disease was noted.
Laboratory data on admission
White blood cell
31.5 × 104/μl
Blood urea nitrogen
We presumptively diagnosed the patient as having advanced diabetic glomerulosclerosis with peculiar extracapillary proliferation. Thereafter, treatment with oral olmesartan medoxomil at 5 mg/day, controlled-release nifedipine at 60 mg/day, and furosemide at 80 mg/day was commenced. The patient also received psychosomatic care for anorexia. Although the patient’s periorbital, arm, and leg edema disappeared over a one month period, his glycemic control worsened with the improvement of his appetite, thus necessitating the use of hypoglycemic agents, including insulin. The patient’s urine protein settled around 1.5 g/g·Cr to 2.0 g/ g·Cr with a slightly elevated serum level of creatinine of 1.7 to 1.9 mg/dl at follow up without any exacerbation of the blood pressure control.
Nodular glomerulosclerosis, which is one of the major pathological findings of diabetic glomerulosclerosis, is a glomerular change characterized by nodular mesangial sclerosis and accentuated glomerular lobularity [9, 10]. Numerous glomerulopathies resemble these morphological alterations when viewed under light microscopy: hypertensive renal disease, light chain deposition induced by a plasma cell dyscrasia, MPGN, and occasionally, amyloidosis . In our case, no etiological linkages between these diseases and the glomerular injuries, except that between hypertension and glomerular damage, were confirmed. Indeed, two glomeruli that were detected on low magnification of renal biopsy specimens obtained from the patient showed collapsed glomerular tufts with wrinkling of the capillary walls and urinary space filled with acellular material, which seemed to be compatible with the features of ischemic glomeruli in hypertensive patients .
Apart from the diagnosis of type 2 diabetes eleven years prior to admission and the results of the ophthalmologic analysis, one may argue that there may have been no clear clinical evidence of diabetes in this patient, since normal values of FBS and HbA1c were noted on admission. However, a transient improvement in glucose metabolism is not exceptional in diabetics with eating disorders . This was the case with this patient, as psychosomatic care for anorexia initiated after the renal biopsy resulted in the gradual deterioration of the patient’s glycemic control, thus necessitating the administration of insulin. The most characteristic immunofluorescent change in diabetic glomerulosclerosis is shown in diffuse linear staining of the glomerular and tubular basement membranes, although this is not necessarily true for all cases with diabetic glomerulopathy and the intensity of such staining varies between individual diabetics. Hyalinosis or exudative lesions often stain brightly with IgM and C3, as demonstrated in our patient [7, 14, 15]. Although the precise process underlying the development of such lesions remains to be delineated, it has been suggested that the development of lesions is associated with endothelial injury and possible hemodynamic alterations . Consequently, it is reasonable to consider that the patient’s low compliance with the overall management of his diabetes and associated complications, such as hypertension, for the long time period prior to his admission may have played a pivotal role in the acceleration of microvascular and endothelial injuries, thus resulting in the various degrees of sclerotic changes compatible with diabetic glomerulosclerosis.
The presence of glomerular electron-dense material and the absence of various serological disorders associated with the development of crescentic glomerulonephritis may indicate the contribution of latent immune-based processes to the development of crescentic glomerular injuries in this patient . However, the hyalinosis or exudative lesions seen in diabetic glomerulosclerosis are also known to be part of an accumulation of homogenous electron dense material . Therefore, it may be difficult to distinguish non-immune hyaline accumulations from granular, electron-dense immune deposits . Nevertheless, the correlations with the clinical, laboratory, and light and immunofluorescence microscopic findings in the current patient do not seem to support the possibility of a superimposed immune-mediated glomerular injury. Instead, the fact that there were varying stages of crescents with exudative lesions compatible with diabetic glomerular injuries shown in the renal biopsy of this patient finally led us to consider that the diabetic glomerular damage could be linked to the formation of crescents, which has been mentioned by a previous study .
In diabetics with overt proteinuria, a diagnosis of diabetic kidney disease can be made in the appropriate clinical setting without pathological confirmation in cases with diabetic retinopathy, a long duration of diabetes, and hypertension . On the other hand, performing a renal biopsy on diabetics has usually been considered when the presence of renal disease other than diabetic kidney disease is suggested by clinical signs, such as the rapid deterioration of renal function, the detection of microscopic or macroscopic hematuria, or the presence of proteinuria in newly diagnosed diabetics without any retinopathy or neuropathy [6, 7]. In this context, the information available concerning the qualitative and quantitative renal morphology of diabetic glomerular injuries seem to involve an intrinsic selection bias [6, 7, 17], and the presence of crescents within the glomeruli damaged by diabetes may therefore sometimes be overlooked especially in the diabetics with potentially advanced diabetic glomerular injuries as demonstrated in the current report. Subsequently, it is not surprising that the etiological linkage between diabetic glomerulosclerosis and the development of crescents has been barely mentioned in previous literature. Nevertheless, such a relationship may not be exceptional [2, 8, 18]. Apparently, the diagnostic and clinical impact of glomerular crescents in patients with diabetic glomerulosclerosis should therefore be evaluated more carefully.
We herein described an unusual case of diabetic glomerulosclerosis with peculiar extracapillary proliferation. Although the etiological linkage between diabetic glomerulosclerosis and the development of crescents has so far only barely been mentioned in previous literature, such a relationship may not be exceptional. Further studies and accumulated experience with renal biopsies are required to better determine the diagnostic and clinical impact of glomerular crescents in patients with diabetic glomerulosclerosis.
Written informed consent was obtained from the patient to publish this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Mathieson PW: The ins and outs of glomerular crescent formation. Clin Exp Immunol. 1997, 110: 155-157.PubMed CentralView ArticlePubMedGoogle Scholar
- Jennette JC: Rapidly progressive crescentic glomerulonephritis. Kidney Int. 2003, 63: 1164-1177. 10.1046/j.1523-1755.2003.00843.x.View ArticlePubMedGoogle Scholar
- Akimoto T, Ando Y, Ito C, Muto S, Kusano E, Asano Y: Effect of plasmapheresis as initial monotherapy in a case of anti-neutrophil cytoplasmic autoantibody positive crescentic glomerulonephritis. ASAIO J. 1999, 45: 509-513. 10.1097/00002480-199909000-00026.View ArticlePubMedGoogle Scholar
- Carstens SA, Hebert LA, Garancis JC, Piering WF, Lemann J: Rapidly progressive glomerulonephritis superimposed on diabetic glomerulosclerosis. Recognition and treatment. JAMA. 1982, 247: 1453-1457. 10.1001/jama.1982.03320350057032.View ArticlePubMedGoogle Scholar
- Ahuja TS, Velasco A, Deiss W, Indrikovs AJ, Rajaraman S: Diabetic nephropathy with anti-GBM nephritis. Am J Kidney Dis. 1998, 31: 127-130. 10.1053/ajkd.1998.v31.pm9428463.View ArticlePubMedGoogle Scholar
- Nasr SH, D'Agati VD, Said SM, Stokes MB, Appel GB, Valeri AM, Markowitz GS: Pauci-immune crescentic glomerulonephritis superimposed on diabetic glomerulosclerosis. Clin J Am Soc Nephrol. 2008, 3: 1282-1288. 10.2215/CJN.00740208.PubMed CentralView ArticlePubMedGoogle Scholar
- Akimoto T, Ito C, Saito O, Takahashi H, Takeda S, Ando Y, Muto S, Kusano E: Microscopic hematuria and diabetic glomerulosclerosis. Clinicopathological analysis of type 2 diabetic patients associated with overt proteinuria. Nephron Clin Pract. 2008, 109: c119-c126. 10.1159/000145454.View ArticlePubMedGoogle Scholar
- Elfenbein IB, Reyes JW: Crescents in diabetic glomerulopathy. Incidence and clinical significance. Lab Invest. 1975, 33: 687-695.PubMedGoogle Scholar
- Schmitz A, Gundersen HJ, Osterby R: Glomerular morphology by light microscopy in non-insulin-dependent diabetes mellitus. Diabetes. 1988, 37: 38-43. 10.2337/diabetes.37.1.38.View ArticlePubMedGoogle Scholar
- Schwartz MM, Lewis EJ, Leonard-Martin T, Lewis JB, Batle D, the collaborative study group, the collaborative study group: Renal pathology patterns in type II diabetes mellitus: relationship with retinopathy. Nephrol Dial Transplant. 1998, 13: 2547-2552. 10.1093/ndt/13.10.2547.View ArticlePubMedGoogle Scholar
- Markowitz GS, Lin J, Valeri AM, Avila C, Nasr SH, D'Agati VD: Idiopathic nodular glomerulosclerosis is a distinct clinicopathologic entity linked to hypertension and smoking. Hum Pathol. 2002, 33: 826-835. 10.1053/hupa.2002.126189.View ArticlePubMedGoogle Scholar
- McManus JF, Lupton CH: Ischemic obsolescence of renal glomerulus: the natural history of the lesions and their relation to hypertension. Lab Invetst. 1960, 9: 413-434.Google Scholar
- Aizawa M, Sakaguchi H, Fukunaga Y, Ashida C, Koshiyama H: A case of non-insulin-dependent diabetes mellitus associated with anorexia nervosa. Intern Med. 1997, 36: 380-10.2169/internalmedicine.36.380.View ArticlePubMedGoogle Scholar
- Olsen JL, Laszik ZG: Diabetic nephropathy. Heptinstall’s Pathology of the Kidney. Edited by: Jennette JC, Olson JL, Schwartz MM, Silvia FG. 2007, Lippincott Williams&Wilkins, Philadelphia, 803-852. 6Google Scholar
- Ainsworth SK, Hirsch HZ, Brackett NC, Brissie RM, Williams AV, Hennigar GR: Diabetic glomerulonephropathy: histopathologic, immunofluorescent, and ultrastructural studies of 16 cases. Hum Pathol. 1982, 13: 470-478. 10.1016/S0046-8177(82)80030-0.View ArticlePubMedGoogle Scholar
- Olson JL, de Urdaneta AG, Heptinstall RH: Glomerular hyalinosis and its relation to hyperfiltration. Lab Invest. 1985, 52: 387-398.PubMedGoogle Scholar
- Mazzucco G, Bertani T, Fortunato M, Bernardi M, Leutner M, Boldorini R, Monga G: Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies. Am J Kidney Dis. 2002, 39: 713-720. 10.1053/ajkd.2002.31988.View ArticlePubMedGoogle Scholar
- Tóth T: Epithelial crescent in diabetic glomeruli. A case report. Int Urol Nephrol. 1987, 19: 347-353. 10.1007/BF02549874.View ArticlePubMedGoogle Scholar
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