1 Section of Nephrology, Department of Internal Medicine, 3 Dipartimento di Scienze Cliniche e Biologiche, University of Turin and 2 SC DiabetologyASO S.Giovanni Battista, Turin, Italy
Correspondence and offprint requests to: Giorgina Barbara Piccoli, MD, Section of Nephrology of the University of Turin, Corso Bramante 8688, 10126 Torino, Italy. Email: gbpiccoli{at}yahoo.it or giorgina.piccoli{at}unito.it
Keywords: diabetes mellitus; kidneypancreas transplantation; nephrosclerosis; pre-emptive transplantation; renal biopsy
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Introduction |
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The present case report is that of a patient referred late to the nephrologist, who performed a renal biopsy because of an atypical course, during the work-up of the patient for a pancreaskidney transplantation. The diagnosis of renal damage, which was that of nephrosclerosis in a patient who was not hypertensive at the time of diagnosis, offers the opportunity to discuss this diagnostic entity, which has been considered with alternative fortunes in the medical literature and has recently been rediscovered as an underestimated cause of chronic kidney disease [25].
This disease, which is a potential cause of end-stage kidney failure, and is considered to be a pre-hypertensive lesion, and not just the result of long-standing hypertension, is interesting because of the predisposing factors associated with it, Including: genetic aspects, subtle alterations in blood coagulation, cigarette smoking, dyslipidaemia, hyperinsulinism and obesity [25].
According to a detailed, expansive search strategy on MEDLINE (1966August 2004) and EMBASE (1988August 2004), that we performed combining the MESH-Emtree and free terms related to diabetes with those related to nephrosclerosis/nephroangiosclerosis, our present report is the first on an association between diabetes mellitus and non-hypertensive nephrosclerosis.
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Case |
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In 1998, she moved to Turin and started an irregular follow-up in our Diabetic Outpatient Care Unit. Her diagnostic work-up revealed normal blood pressure (110130/7085 mmHg) and pre-proliferative diabetic retinopathy, in the absence of autonomic neuropathy, dyslipidaemia and cardio-vasculopathy; in addition, severe kidney failure was confirmed. She did not have a history of hypertension, and was normotensive at all the clinical visits, which were, however, somewhat irregular, which had been performed in diabetology, during pregnancy and during hospitalizations.
She was hospitalized in the Nephrology ward for a diagnostic evaluation and the initiation of work- up for a pancreaskidney graft. On admission, her serum creatinine was 4.5 mg/dl, creatinine clearance 16 ml/min, proteinuria 0.8 g/24 h, cholesterol 204 mg/dl (high-density lipoprotein = 48 mg/dl) and triglycerides 113 mg/dl. Renal ultrasound and Doppler ultrasonography showed kidneys of normal size, with sinusal sclerolipomatosis and bright thin cortices (longitudinal diameter: left, 10 cm; right, 11 cm), without signs of arterial stenosis, but with a bilateral increase of the arterial resistance index. A renal scintiscan showed symmetrically reduced parenchymal phases without signs of obstruction. Proteinuria was non-selective, and microscopic urinalysis showed 35 red blood cells per high power field (400x), with rare hyaline casts. A renal biopsy was performed in view of the patient's atypical course and the preserved kidney size. On light microscopy, 20 glomeruli were seen, 11 of which had global ischaemic glomerulosclerosis (the other nine had diffuse collapsing of the basal membranes), with tubular atrophy, interstitial fibrosis and myo-intimal hyperplasia (Figure 1). We made the diagnosis of nephrosclerosis without evidence of diabetic nephropathy.
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Discussion |
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The finding of nephrosclerosis was unexpected in this young, non-hypertensive woman. It may support the idea, suggested by Meyrier and Simon, that this condition may be underdiagnosed, due to the habit of reserving the renal biopsy procedure for patients whose clinical and urinary picture (proteinuria, active urinary sediment, haematuria) is suggestive of a glomerular disease potentially amenable to some kind of therapy [2].
Indeed, while relatively rare situations (such as isolated nocturnal hypertension) could not be ruled out completely in her case, since 24 h blood pressure monitoring was not performed, she was always normotensive at her out-patient visits and during her hospitalizations, a pattern that is in disagreement with the usual history of patients with hypertensive nephrosclerosis, which is dominated by high blood pressure levels, over years or decades.
While the typical lesions of nephrosclerosis may actually precede the development of hypertension, at least in some high risk ethic subgroups, as they do in animal models [7], cigarette smoking was the only putative risk factor, beside diabetes, that was present in this young woman.
Smoking has been implicated in the development and progression of chronic kidney disease, particularly with regard to its detrimental effect on renal vasculature. The link with primary nephrosclerosis is putative. It was originally postulated by Meyrier and Simon in a pivotal paper on this topic [2], and it recently was widely discussed, with somwhat conflicting results. While some studies suggest that the renal damage caused by smoking is mainly confined to the small interlobular arteries, its effect on the vasculature throughout the body appears to be enhanced by diabetes. The combination of the two is so noxious as to render the prognosis of diabetics who smoke abysmal [8,9]. Conversely, smoking is considered a potent risk factor in the development of nodular glomerulosclerosis, a picture similar to that of diabetic glomerulosclerosis, but occasionally also found in non-diabetics [10]. The extension of the biopsy policy to include non-hypertenive, non-proteinuric patients might lead to additional insights in this debated field.
In summary, this case may suggest considering the differential diagnosis of primary nephroangiosclerosis also in young, normotensive patients, and it calls for attention to the possible facilitating effect of diabetes per se, eventually enhanced by cigarette smoking.
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Acknowledgments |
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Conflict of interest statement. None declared.
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References |
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