Predicting non-diabetic renal disease in type 2 diabetic adults: The value of glycated hemoglobin

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Abstract

Aims

The indications for renal biopsy in type 2 diabetes mellitus (T2D) are not well established. We investigated the prevalence, spectrum, and predictors of biopsy-proven non-diabetic renal disease (NDRD) in T2D.

Methods

An observational, single-center, retrospective study of T2D adults who underwent renal biopsies (N = 51) over 10 years for nephrotic-range proteinuria, microscopic hematuria, or rapidly declining renal function.

Results

Thirty-five (68.6%) biopsies were diagnostic of NDRD, and 16 (31.4%) revealed isolated diabetic nephropathy. The most common NDRDs were interstitial nephritis (20%), progressive crescentic glomerulonephritis (14%), membranous nephropathy (11%), and focal segmental glomerulosclerosis (11%). The odds for NDRD declined by 97% in the presence of diabetic retinopathy (P < 0.001). The deterioration of HbA1c during the year before biopsy predicted NDRD even after adjusting for diabetic retinopathy (OR, 7.65; 95% CI, 1.36–123.04; P = 0.003). A model based on the interaction between the HbA1c values 12 months before biopsy and the absolute change in these values during the preceding year predicted NDRD with 73.7% sensitivity and 75% specificity (AUC, 0.77; 95% CI, 0.59–0.94).

Conclusions

This study demonstrated a considerably high prevalence of NDRD in T2D adults undergoing renal biopsy. The absence of diabetic retinopathy, lower HbA1c values 12 months before biopsy and greater deterioration in HbA1c prior to biopsy predicted NDRD in T2D. Further studies are needed to validate the findings.

Introduction

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus associated with end-stage renal disease requiring renal replacement therapy. A major contributor to development and progression of DN is glycemic control as shown by major diabetes studies (Stratton et al., 2000, The Microalbuminuria Collaborative Study Group, 1999). Other modifiable factors for DN include hypertension, obesity, smoking, and dyslipidemia (Gross et al., 2005). There is encouraging evidence suggesting that timely and long-term tight glycemic control effectively delays the onset and slows the progression of DN in both type 1 and type 2 diabetes (The Diabetes Control and Complications Trial Research Group, 1993, UK Prospective Diabetes Study (UKPDS) Group, 1998).

The diagnosis of DN is usually made through biochemical analyses of urine and blood. An early manifestation is persistent microalbuminuria. Estimated glomerular filtration rate (eGFR) declines prior to more severe macroalbuminuria in type 2 diabetes (T2D); hence a combination of eGFR and albuminuria can be used to stage and monitor patients (American Diabetes Association, 2013, Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group, 2013). While diabetes is the major cause of renal disease in patients with diabetes, in about a third of patients, renal dysfunction is due to other causes (non-diabetic renal disease; NDRD) (Chong et al., 2012, Das et al., 2012, Harada et al., 2013, Kleinknecht et al., 1992, Lee et al., 1999, Mazzucco et al., 2002, Olsen and Mogensen, 1996, Richards et al., 1992, Soni et al., 2006, Yaqub et al., 2012). In the NDRD group, the treatment of renal disease may require a different strategy. A renal biopsy is helpful in determining the underlying pathophysiology in NDRD.

The selection criteria for renal biopsy in diabetic patients are not well established. In type 1 diabetes, the presence of proteinuria with short diabetes duration and/or rapidly declining renal function, especially in the absence of diabetic retinopathy, has been suggested as a signal for the need for renal biopsy (Mauer, Fioretto, Woredekal, et al., 2001). In T2D, the criteria are less clear since dysglycemia is present for many years prior to diagnosis. Commonly, proteinuria > 1 g/24 hours, renal involvement without diabetic retinopathy, or unexplained hematuria has been used as indicators for renal biopsy (Wong, Choi, Szeto, et al., 2002). Identification of novel predictors of renal disease will improve the current selection criteria for renal biopsy and facilitate early detection of NDRD in T2D. Early diagnosis and appropriate treatment may help slow progression to end stage renal disease. In this study, we sought to investigate the prevalence, spectrum, and predictors of biopsy-proven NDRD in adults with T2D.

Section snippets

Subjects, material and methods

This was a retrospective observational study of T2D patients who underwent renal biopsies over 10 years in our center. As this was an audit of retrospective data, the local research ethics committee felt that no formal ethics approval was required.

Fifty-one native renal biopsies obtained from 51 adults with a documented diagnosis of T2D, referred to our center between 2002 and 2012, were analysed. In our center, as a policy, DN is diagnosed on clinical grounds and kidney biopsies are only

Sample characteristics and renal biopsy findings

The entire cohort of renal biopsy patients (N = 51) was predominantly male (64.7%), of mixed ethnicity (28 White Europeans, 18 South-Asians, 3 African Caribbean, 2 with “not stated” ethnicity), aged 61 ± 12 years (mean ± SD). The median (IQR) duration of T2D was 9 years (2–15 years) (n = 45). At the time of renal biopsy, the NGSP HbA1c was 7.2% (6.4–7.8%), the IFCC HbA1c 55 (46–62) mmol/mol (n = 42). Twenty-two of 39 (56.4%) patients had diabetic retinopathy. The median (IQR) eGFR was 23.5 ml/min/1.73 m2

Discussion

There were three major findings in the present study. First, renal biopsies with histological confirmation of renal involvement revealed a considerably high prevalence of NDRD in a cohort of T2D patients with significant dipstick hematuria, nephrotic range proteinuria, and/or rapidly declining renal function. Second, this study confirmed the previously recognized associations between poor long-term glucose control and presence of diabetic retinopathy and DN in T2D (Stratton et al., 2000).

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    Conflict of Interest: MP has received grant/research support from Slovakian Diabetes Association/Lilly Diabetes Clinical Research Initiative. AM, GL, ST and ID declare that they have no competing interests.

    1

    The permanent address of Maria Pallayova: Department of Human Physiology, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic.

    2

    The present address of Azharuddin Mohammed: Renal Unit, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3NE, UK.

    3

    The present address of Shahrad Taheri: Department of Medicine, Weill Cornell Medical College in Qatar, PO Box 24144, Doha, Qatar.

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