Predicting Patients With Nondiabetic Renal Disease

The Big Diabetes Lie

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Obviously some diabetic patients will develop non-diabetic renal disease. Therefore, are there any clinical parameters that clinicians can use to predict non-diabetic renal disease in a population that has high rates of renal insufficiency and abnormal urinary sediment? Several clinical parameters have been reported to predict a high rate of non-diabetic renal disease.


Haematuria occurs in diabetic nephropathy in over 50% of cases. Nevertheless some authors have suggested that its presence predicts non-diabetic disease. For example, in a Chinese population, in whom rates of IgA nephropathy were predictably high, the presence of haematuria was useful in predicting non-diabetic disease [12]. In contrast, in the series of 136 proteinuric diabetic patients who underwent biopsy described by Taft et al [21], 66% had microscopic haematuria. The presence or absence of microscopic haematuria did not help to predict whether the patient had non-diabetic renal disease.

Generally haematuria is not a strong predictor of non-diabetic glomerular disease but it may be a sign of lower tract disease. In older patients without associated proteinuria, the presence of haematuria warrants imaging of the renal tract and cystoureteroscopy, as indicated for non-diabetic patients.

Absence of retinopathy

The absence of retinopathy has different implications in type 1 and type 2 diabetes. In type 1 diabetes there is a very close association between retinopathy and nephropathy. The absence of retinopathy, assessed formally by photography or angiography, in a type 1 diabetic with abnormal renal function or proteinuria would be an indication to biopsy the patient if no other cause of renal disease was evident.

The situation is less clear in type 2 diabetes. Many patients with type 2 diabetes do not have classical histological changes of diabetes but nevertheless their renal disease is related to their diabetes. The presence of retinopathy strongly predicts the presence of typical diabetic glomerular changes [4,5,31], in particular Kimmelsteil-Wilson nodules [11]. What is less clear is how useful is its absence in predicting non-diabetic disease. Parving et al suggested that the absence of retinopathy strongly predicted non-diabetic renal disease in macroalbuminaemic type 2 diabetics [3]. Christensen et al described the biopsy findings from 52 type 2 diabetics with microalbuminuria but absent retinopathy (defined by fundal photography) [16]. Most patients had diabetic nephropathy but non-diabetic disease was found in 7 patients (13%) and normal glomerular structure in a further 9 patients (18%). Therefore although the presence of retinopathy indicates diabetic nephropathy, even in its absence the patient is likely to have diabetic kidney disease.

Rapid decline in renal function

The course of diabetic nephropathy has been extensively described. A rapid decline in renal function (perhaps >10% of residual function per month) in a normotensive diabetic is inconsistent with diabetic disease and is an indication for further assessment and biopsy.

Nephrotic syndrome

The course of diabetic nephropathy, with microalbuminuria preceding heavier proteinuria and nephrotic syndrome, is well documented, particularly in type 1 diabetes [32]. Patients who develop significant, nephrotic range proteinuria without preceding microalbuminuria despite appropriate testing should be considered for biopsy. For patients who develop lesser degrees of proteinuria (for example <1g/24 hours) the case for biopsy is less clear. In the absence of positive serology, reduced GFR or hypertension there is no consensus as to whether biopsy is indicated for any patient with this level of proteinuria irrespective of whether they are diabetic.

Short duration of diabetes

The clinical course of type 1 diabetes is usually predictable with diabetes diagnosed many years before the onset of diabetic nephropathy. In contrast, type 2 diabetics may present with established microvascular complications. Therefore a short duration of diabetes prior to the development of abnormal renal functional parameters is highly predictive of non-diabetic renal disease in type 1 diabetes. This is not the case in type 2 diabetes where, in general, studies show no correlation between duration of diabetes and the presence of non-diabetic renal disease [2,3,12,16,18].

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