Diabetes Res Clin Pract. 2013 May;100(2):E39-E41.

Clinical features associated with a rapid decline in renal function among Japanese patients with type 2 diabetes mellitus: Microscopic hematuria coexisting with diabetic retinopathy.

Kajiwara A, Sakata M, Kita A, Morita K, Oniki K, Saruwatari J, Yoshida A, Jinnouchi H, Nakagawa K. kazukon@gpo.kumamoto-u.ac.jp

Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences & Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Jinnouchi Clinic, Diabetes Care Center, Kumamoto, Japan.



This retrospective case study aimed to identify the clinical features associated with a rapid decline in renal function in Japanese patients with type 2 diabetes mellitus (T2DM). Among 320 patients with T2DM and normal renal function: estimated glomerular filtration rate (eGFR) over 60 ml/min/1.73 m2 and no urinary abnormality at baseline, four cases exhibited a decline in the eGFR to below 30 ml/min/1.73 m2 during a median follow-up time of 6.8 years, with the rate of decline being 12.3 – 23.5 ml/min/1.73 m2/year (Figure 1). All of these patients had marked albuminuria and developed persistent microscopic hematuria while the eGFR was preserved [68.9 – 107.2 ml/min/1.73 m2]. Other common features of these patients included poor glycemic control [HbA1c 8.6 – 12.0%], incomplete control of hypertension (100%), the presence of diabetic retinopathy (DR) (75%), increased intima-media thickness (75%, no data in one case), being overweight (75%), an ever-smoking status (75%) and poor medication adherence (100%) (Table 1). The present cases highlight the need for more extensive use of renal biopsies irrespective of the presence of DR, in order to identify the pathology and to prevent progression, and also the need for education and support programs to improve medication adherence in daily practice.

PMID: 23433540



The renal injuries in patients with diabetes include diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD).1-4 A recent meta-analysis identified that the absence of DR, a shorter duration of diabetes, a lower HbA1c and lower blood pressure may help to distinguish NDRD from DN in patients with diabetes.1 Another meta-analysis also indicated that the presence of DR is useful for diagnosing or screening for DN in patients with T2DM and renal disease.2 On the other hand, renal biopsies help to classify renal diseases into three groups associated with different prognostic features: DN, NDRD and superimposed NDRD on underlying DN.3,4 The major indications for renal biopsy are signs suggesting NDRD, such as a rapid onset of proteinuria, the presence of hematuria, a rapid decline of renal function and a lack of DR.4 However, there are currently no standardized criteria for performing a renal biopsy in patients with T2DM; therefore the decision to perform one is made by the primary physician.4

Kazuko Nakagawa-1

All four cases who exhibited a large decline in the eGFR in this study developed persistent albuminuria and microscopic hematuria while the eGFR was preserved (Figure 1). These cases also had common risk factors for DN, including DR, a high HbA1c and poor medication adherence (Table 1), thus, they did not undergo renal biopsies. In the cases without diabetes, concomitant hematuria and proteinuria are established risk factors for renal insufficiency and signs of IgA nephropathy.4 NDRD has been reported in 14 – 83% of patients with T2DM who undergo renal biopsies and the most common NDRD found across reports in the literature is IgA nephropathy.3,4 Furthermore, IgA post-infectious glomerulonephritis is becoming more common, and often occurs in adults who are diabetic.5,6 Moreover, there is a clear relationship between the degree of hyperglycemia and the severity of periodontitis, which negatively affects both DN and NDRD.7,8 Therefore, it is important to identify and differentiate these pathologies at an early stage in order to prevent their progression and the potential development of complications. The present cases suggest that the presence of concomitant hematuria and proteinuria while the eGFR was preserved may be a key factor for decision-making regarding whether a renal biopsy should be performed, irrespective of the presence of DR.

Kazuko Nakagawa-2


  1. Liang S, Zhang XG, Cai GY, Zhu HY, Zhou JH, Wu J, Chen P, Lin SP, Qiu Q, Chen XM. Identifying parameters to distinguish non-diabetic renal diseases from diabetic nephropathy in patients with type 2 diabetes mellitus: a meta-analysis. PLoS ONE 8: e64184, 2013.
  2. He F, Xia X, Wu XF, Yu XQ, Huang FX. Diabetic retinopathy in predicting diabetic nephropathy in patients with type 2 diabetes and renal disease: a meta-analysis. Diabetologia 56: 457-466, 2013.
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  6. Nasr SH, Fidler ME, Valeri AM, Cornell LD, Sethi S, Zoller A, Stokes MB, Markowitz GS, D’Agati VD. Postinfectious glomerulonephritis in the elderly. J Am Soc Nephrol 22: 187-195, 2011.
  7. Chee B, Park B, Bartold PM. Periodontitis and type II diabetes: a two-way relationship. Int J Evid Based Healthc 11: 317-329, 2013.
  8. Chambrone L, Foz AM, Guglielmetti MR, Pannuti CM, Artese HP, Feres M, Romito GA. Periodontitis and chronic kidney disease: a systematic review of the association of diseases and the effect of periodontal treatment on estimated glomerular filtration rate. J Clin Periodontol 40: 443-456, 2013.

Kazuko Nakagawa-3

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