The global and the local increase in T2DM prevalence could be attributed to many factors including; genetic predisposition, the change in lifestyle and diet, the presence of risk factors, and to uncontrolled diabetes [3] [1]. Chronic kidney disease is one of the serious consequences to uncontrolled diabetes [12]. To the extent of our knowledge, this is the first study in Jordan that evaluated kidney functions in T2DM patients using the eGFR MDRD formula, it also identified people at risk of future kidney diseases. The kidney damage predictors are very important, they act as an alarm to warn the T2DM patient of future kidney failure if untreated [8].
The eGFR is a widely used indicator to assess kidney functions, it is also considered a strong predictor for the progression to CKD and ESRD [23] [28]. The eGFR reflects to some extent the measured GFR (mGFR), hence it is easier and faster to use [23] [28]. The eGFR values were compared to mGFR in several studies, some of them found it representative, others found it overestimating or underestimating. In the study that compared the eGFR to mGFR in nondiabetic patients, they found that the eGFR underestimated the mGFR by 28% per year [29]. A contrast study was performed on patients with polycystic kidney diseases suggested that the eGFR slope overestimated the decline in the mGFR by 1.5% per year [30]. When the eGFR formula was performed on diabetic subjects who developed diabetic nephropathy, they found that the eGFR underestimated the mGFR decrement by 1.2 ml/min per 1.73 m2 per year. Suggesting that the use of eGFR in an advanced stage of diabetic nephropathy is less informative regarding the actual situation among diabetic patients [31]. Nevertheless, the eGFR is still considered a good tool to predict future kidney failure in T2DM patients as reported by Belguith, Taderegew, and Vincent [28] [23] [19]. In agreement with the previous studies, we found that most of the T2DM patients had their eGFR values less than 90 mL/min per 1.73 m2, with evidence of kidney malfunction (proteinuria). Interestingly, the amount of protein in urine increases with the decrease in eGFR value (Tables 4). Similar findings were reported in a previous study by Belguith H, who used the MDRD eGFR formula to evaluate kidney functions in diabetic patients in Saudi Arabia [28]. Though, the Belguith study did not provide information about proteinuria or the ACR level in their study [28]. We also found that most of the T2DM patients were in the S2 CKD category, which also agreed with Belguith’s findings [28]. Nevertheless, we found that more than 22% of the T2DM patients had their eGFR less than 60 ml/min per 1.73m2 compared to 29% and 19% in Belguith H, and Taderegrew M studies, respectively [28] [23]. This difference could be attributed to the sociodemographic of the T2DM patients, the sample size, and maybe to the measured sCr level and other biomedical variables that were involved in calculating the eGFR formula.
Of note, we found that male T2DM patients had a higher prevalence of abnormal biochemical variables and eGFR values than females, which reflected a higher chance of developing CKD diseases in the future compared to females. This result is consistent with Abdullah and his colleagues’ study that was performed in Jordan on patients who undergo hemodialysis. They found that most of the patients at the hemodialysis unit had diabetes, the majority were males [11].
Previous studies confirmed that tight glycemic control can slow down the progression to diabetic nephropathy and the progression to ESRD [32] [33]. The uncontrolled T2DM is more common among low-income, uneducated, and unemployed people [34]. Herein, most of the T2DM patients especially males had uncontrolled diabetes according to their FBS and HbA1C values, which is really a threat to their kidney health. T2DM patient sociodemographic like age, income, and education level, in addition to the follow up with the diabetic clinic and the regular use of diabetic medications, they all together participate in keeping a controlled glycemic level. Diabetic patients have to be counseled and well educated in order to help them to control their diabetes as patients education and self-management programs are important preventive approaches for the progression of CKD.
In harmony with previous studies, we found that the eGFR values were negatively correlated with the T2DM onset duration [23] [35]. We also detected a negative correlation between eGFR and patients’ serum creatinine and proteinuria. This result was reported earlier by Nelson and his colleagues, they found that the increase in serum creatinine level was associated with a decrease in eGFR and CKD stages progression [36]. The presence of proteinuria was also associated with the decrease in eGFR. The same finding was reported in a study from Japan, they found that the eGFR value from subjects with proteinuria was lower than that in subjects without proteinuria [37]. The increase in serum creatinine and the presence of proteinuria are considered a strong predictors of reduced kidney functions.
Many studies were oriented towards finding a correlation between the different biochemical variables like FBS, HbA1C, serum creatinine, and proteinuria in T2DM patients. Herein, we detected interesting positive correlation between the T2DM patients’ biochemical variables which confirmed previous findings. The HbA1C level was significantly increased with the increase in the duration of T2DM [38]. We detected a moderate correlation between the HbA1C and the FBS level in T2DM patients [39] [40]. Emphasizing previous findings, we noted that the serum creatinine level is associated with HbA1C [41] [42]. The urine ACR is considered an important marker of kidney damage in T2DM patients, we found that the ACR value is significantly correlated to HbA1C in diabetic patients, which confirm the previous findings by Haque and Sivasubramanian [42] [43].
A captivating finding we had was the association of proteinuria with FBS, and HbA1C (blood sugar). Two years follow-up study by Bahar and his colleagues on prediabetes patients who had microalbuminuria, found a significant number of the prediabetic patients who had proteinuria progressed to diabetes [44]. A similar finding was reported by Tatsumi Y [45]. These findings emphasized the early association of proteinuria and the glycemic status in T2DM patients from one side, and the importance of measuring the presence of proteinuria as a predictor of kidney damage on the other side. We also detected a moderate association between PU and sCr in T2DM patients. This association was confirmed in Karar T, et al study [40], and contradicted in Sanyal M, et al study [46]. Sanyal and his colleagues found no significant association between the two chemical parameters [46]. This could be attributed to the sample size, the sociodemographic, and the clinical picture of the T2DM patients, the risk factors and presence of diabetic nephropathy also contributed to this difference. More research has to be conducted in this regard to confirm and reveal the mechanism behind this association at the molecular level. Among the worthy findings we had were the strong association between PU and the ACR, and the moderate association between ACR and sCr in T2DM patients. Similar findings were found by Karar and his colleagues’ study [40].
Amid the available eGFR formulas, we used the MDRD because it is more accurate in predicting renal failure, also it doesn’t need patients’ weight information compared to Cockcroft-Gault (CG) formula [19]. The eGFR value is an easy screening method that reflects kidney health compared to mGFR. A new approach that gives a better prediction and assessment for eGFR value is based on Cystatin C rather than sCr. The Cystatin C protein is an endogenous marker of renal functions that produced by cells in a constant amount, it is serum concentration doesn’t depend on muscle mass, weight, age, or gender like the creatinine-based formulas. A comparison study showed that Cystatin C protein is a better predictor of kidney functions compared to creatinine in T2DM patients [47]. Future studies that use Cystatin C are recommended to assess kidney functions in T2DM patients.