Catherine Lasseur

Bone loss in diabetic patients with chronic kidney disease

Objective  We investigated whether loss of bone is detectable during follow‐up of diabetic patients with chronic kidney disease (CKD).

Progression-related bias in the monitoring of kidney function in patients with diabetes and chronic kidney disease.

The Cockcroft and Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations underestimate the glomerular filtration rate (GFR) decline in diabetes. Do this decline and the albumin excretion rate (AER) influence their validity? In 161 diabetic patients, isotopically determined GFR (i-GFR) (51Cr-EDTA) was compared with estimated GFR (e-GFR) by the CG, MDRD, and the new Mayo Clinic Quadratic (MCQ) equations. We searched for a relation between the error in e-GFR and the AER. An influence of the AER outcome on the e-GFR decline was evaluated in 63 subjects followed up over 3 years. The MDRD and the MCQ were more precise and accurate than the CG, but they were biased. The error increased with AER for the CG (r = 0.25, P = .001) and the MDRD (r = 0.20, P = .009), but not for the MCQ. For the 63 patients followed up, the e-GFR declines by the 3 estimations were related to the initial AER, whereas no relation with arterial blood pressure, hemoglobin A(1C), hemoglobin, and blood lipids emerged. The MCQ declines were more pronounced: -10.5% +/- 8.9% in the macroalbuminuric group (P < .05 vs both microalbuminuric [-2.6% +/- 10.1%] and normoalbuminuric [-0.1% +/- 6.6%] groups), and were related to the outcome of the AER (r = 0.33, P < .05). As chronic kidney disease progresses in diabetes, the declining GFR and rising AER influence the estimation of GFR by the CG and MDRD equations, underestimating the GFR decline and the benefit of reducing the AER. The less affected MCQ evidences a slower e-GFR decline with AER control.

Normoalbuminuric chronic kidney disease in type 1 diabetes: is it real and is it serious?

To the Editor: We were interested by the recent article by Penno et al, who reported that the majority (17/29) of their participants with stage ≥3 chronic kidney disease (CKD) and type 1 diabetes had the non-albuminuric phenotype (Alb; albuminuria <3.4 mg/mmol) [1]; this is an unexpectedly high proportion. As reported by the authors, these participants had higher Modification of Diet in Renal Disease (MDRD) Study equation-estimated GFR (eGFR) (52 ± 7 ml min [1.73 m]) vs those with the albuminuric phenotype (Alb; albuminuria ≥3.4 mg/mmol), who had an eGFR of 45 ± 11 ml min [1.73 m] (p < 0.05); this was not commented on to a great extent in the article. Two hypotheses may explain this less advanced renal failure in the Alb group. First, participants with Alb phenotype may not really have CKD. Although it works better than the old Cockcroft and Gault formula [2], the MDRD equation was built by multiple regression analysis from a population with renal insufficiency, and it is well-known to underestimate normal and high GFR: according to the analysis from Froissard et al, 20.5% of MDRD equation-estimated stage 3 CKD was, in fact, stage 2 CKD based on Cr-EDTA analysis [3]. Penno et al recognised that estimation by the MDRD equation was a limitation of their study [1]. To investigate whether the higher MDRD equationdeduced eGFR in the Alb group might have resulted from such underestimated eGFR, we compared the MDRD equation-eGFR to isotopically measured GFR (mGFR), analysed using Cr-EDTA, in 40 individuals with type 1 diabetes and MDRD equation-eGFR below 60 ml min [1.73 m]. Participants included 21 men (52.5%) aged 57 ± 13 years old, with a median albumin excretion rate (AER) of 189 mg/24 h (range 5–2500). Only three individuals had the Alb phenotype. In our participants, the MDRD equation-eGFR was 41.7 ± 12.4 ml min [1.73 m], which was similar to the mGFR (42.0 ± 21.9 ml min [1.73 m]). Regarding eGFR, individuals with stage 3a CKD in our study (n = 22) were similar to the individuals with stage 3 CKD in the study by Penno et al [1], and their MDRD equation-eGFR did not differ from mGFR (MDRD equation-eGFR: 51.1 ± 3.7 ml min [1.73 m]; mGFR: 50.7 ± 15.1 ml min [1.73 m]) (unpublished results, V. Rigalleau). As demonstrated using data from the DCCT, in the 60–80 ml min [1.73 m] MDRD equation-eGFR range, ~80% of eGFR values may be underestimated by more than 20 ml min [1.73 m] as compared with the iothalamate clearance method [4]. This may explain the large number of individuals with MDRD equation-eGFR 60–74 ml min [1.73 m] in Penno et al’s study who were categorised as Alb (n = 63) vs Alb (n = 8). However, this does not seem to explain the high number of individuals with the Alb phenotype with stage 3 CKD, who were probably highly renal insufficient. * Vincent Rigalleau vincent.rigalleau@chu-bordeaux.fr

Prediction of mortality rate in type 2 diabetes: estimated glomerular filtration rate underestimates the true rate

To the Editor: In their paper published in Diabetologia [1], Bruno et al. assessed whether a reduction in estimated glomerular filtration rate (eGFR), calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) study equation [2], predicted mortality in type 2 diabetes. Although an eGFR of <60 ml min 1.73 m was associated with a twofold increase in the mortality rate, further analyses using smaller eGFR categories (15–29, 30–44, 45–59 ml min 1.73 m) revealed that this was due to the increased risk in patients with eGFR values between 15 and 29 ml min 1.73 m, with hazard ratios even suggesting a benefit for the non-proteinuric, moderate renal failure strata. To investigate whether this unexpected finding was due to the inaccuracy of the abbreviated MDRD equation in estimating GFR, we compared eGFR values with GFR values determined by Cr-labelled EDTA clearance (isotopic GFR [iGFR]) in a group of volunteers, stratifying the results as per Bruno et al. [1]. In total, 128 patients with type 2 diabetes (age 67±9 years, BMI 28.8±4.8, HbA1c 8.5±1.6% [data presented as means ± SD], 53 women) gave informed consent to participate in this study, which was conducted in accordance with the Declaration of Helsinki. In the group as a whole, iGFR was 54.5±32.7 ml min 1.73 m. Although the eGFR (48.2±18.8 ml min 1.73 m) showed a strong correlation with i-GFR (r=0.80, p<0.001), it underestimated it (p<0.001). The comparisons of eGFR and iGFR for each eGFR stratum as defined by Bruno et al. are shown in Table 1. In the group as a whole, most of the subjects (55.5%) were wrongly classified by the MDRD-estimated GFR in the four GFR strata. This suggests that the majority of patients followed by Bruno et al. would have been classified in other strata if measured GFR rather than eGFR values had been used. In particular, many patients in the 45–60 and 60–89 ml min 1.73 m eGFR intervals, who had hazard ratios of <1.00 for all-cause and cardiovascular mortality in the paper [1], would have been in higher GFR strata. Although it is the best predictor of GFR in diabetic patients with renal insufficiency [3], the MDRD equation is well known to underestimate GFR values at the upper end of the normal range [4]. This explains the high proportion of patients with chronic kidney disease in the population Diabetologia (2007) 50:2410–2411 DOI 10.1007/s00125-007-0796-8