Discussion
This is the first study to elucidate the impact of the severity of hypertension on the initiation of dialysis in people with and without DM in a large-scale longitudinal setting. The risks for the initiation of dialysis in those with DM+ and SBP ≤119 mmHg were equivalent to those with DM- and SBP ≥150 mmHg, indicating that the presence of DM could indicate the need for more strict blood pressure interventions to avoid dialysis. Also, the risks of hypertension were not very different between those with and without DM. The risk of the initiation of dialysis was almost seven times greater in those with both DM+ and hypertension compared with DM- and non-hypertension. However, we could not use the renal function as a covariate, and SBP was measured at only one point in time. Further studies are needed to confirm our findings considering those important risk factors for the initiation of dialysis.
Recently, more strict blood pressure targets were recommended in accordance with the change in the definition of hypertension from ≥140/90 to ≥130/80 mmHg in the ACC/AHA guidelines. However, the target value for hypertensive individuals to avoid dialysis is still unknown. Although DM and hypertension defined as SBP ≥140 mmHg, DBP ≥90 mmHg or antihypertensive treatment are well-known risk factors for ESRD defined as initiation of renal replacement therapy [3], no evidence was established for the prevention of dialysis according to DM status. Our findings demonstrated that SBP ≥140 mmHg was a significant independent predictor for the initiation of dialysis in people without DM, whereas this level increased to SBP ≥150 mmHg in people with DM. However, the risk for the initiation of dialysis for DM+ and, especially, SBP ≤119 mmHg was almost the same as that for DM- and hypertension, especially with SBP ≥150 mmHg. This indicates that people with DM could need more severe blood pressure interventions to prevent dialysis. However, further studies are needed to confirm our findings including other risk factors such as the duration of hypertension and the eGFR.
Generally, hypertension is a well-known risk factor for renal dysfunction [1]. However, little is known about whether the associations also apply to ESRD, and especially whether such associations also apply to renal replacement therapy, not only ESRD, among people with and without DM. The risk of CKD defined as the requirement for dialysis or transplantation or by the notation of kidney disease on the death certificate and confirmed by medical record review significantly increased from SBP ≥160 mmHg, compared to SBP <120 mmHg with adjustment for DM [4]. Also, the risk of ESRD defined as receipt of renal transplantation or maintenance dialysis increased along with the SBP level after adjustment for DM [5]. Hypertension is a well-known risk factor for renal dysfunction in patients with DM [11-13], and SBP ≥120 mmHg could be associated with development of nephropathy in patients with DM [14]. SBP reportedly predicts early onset of doubling of serum creatinine concentration or ESRD defined as dialysis or renal transplantation in diabetic patients with nephropathy [15]. Higher SBP increases a risk of ESRD among Japanese people with and without DM [6]. Hyperglycemia defined as fasting blood glucose ≥126 mg/dl (7.0 mmol/L) is a risk factor for the development of ESRD in a Japanese general population [7]. However, that study did not evaluate the impact of the combination of the SBP cut-offs and the presence or absence of DM on starting dialysis. Hsu et al. [5] showed that all of the stratified SBP values in DM+ had higher impacts on ESRD defined as receipt of renal transplantation or maintenance dialysis than in DM-. These findings are consistent with our results suggesting that elevated SBP is a useful marker for predicting initiation of dialysis as well as DM. However, these studies [4.5] did not adjust for antihypertensive medications as a covariate. Moreover, although HbA1c is the gold standard for reflecting hyperglycemia [16] in clinical settings to evaluate the risk of initiation and development of nephropathy [17-19], that study [5] did not use HbA1c to define DM and adjusted only for age. Moreover, we showed that the risk of initiation of dialysis with DM+, even at SBP ≤119 mmHg, was almost the same as such a risk according to DM- and SBP ≥150 mmHg.
Intensive lowering of SBP increased the risk of eGFR loss with and without DM. In addition, this risk was higher in people with DM [20]. At the same time, strict control of blood pressure increased renal dysfunction due to decreased renal blood flow in patients with DM, especially with progressive atherosclerosis [21]. On the other hand, patients with DM might benefit from intensive lowering of blood pressure regarding CVD risk [22]. Therefore, future studies are needed to conclude the optimal cut-off level of SBP for the initiation of dialysis.
Our present study’s strengths were its large sample size and accurate definitions of DM, hypertension, and dialysis based on data from health examinations and a claims database that included information on medical practice, which allowed for the certainty that patients with DM had diabetes and to identify almost all patients who underwent initiation of dialysis during the follow-up.
Our study also had some limitations. First, we could not use the eGFR or proteinuria as a covariate. Unfortunately, serum creatinine level is not always included in medical health checkups in Japan, and there were much missing data on proteinuria. Therefore, further studies are needed to confirm our findings considering those important risk factors for the initiation of dialysis. Second, we were unable to distinguish between type 1 and 2 diabetes. Second, it was also not possible to identify distinction between type 1 and 2 diabetes patients be ascertained. However, type 2 diabetes is more common than type 1 diabetes and accounts for 95% of diabetes in Japan. Although renal anemia according to the progression of renal failure could affect the HbA1c level, HbA1c was widely used as the glycemic index in clinical practice even among patients with chronic renal failure [23]. Third, we do not include renal transplantation as an endpoint in this study. However, the influence of excluding renal transplantation from the analysis would be minimal because the incidence of renal transplantation is very low in Japan. Fourth, it was not possible to identify participants whose glucose control had either improved or deteriorated during the follow-up period. Also, SBP was measured at only one point in time.
In conclusion, although the risks of hypertension were not very different between DM+ and DM-, the risks for the initiation of dialysis in those with DM+ and SBP ≤119 mmHg were equivalent to those with DM- and SBP ≥150 mmHg, indicating that individuals with DM could need more strict blood pressure interventions to avoid dialysis. Future studies are needed to conclude the cut-off level of SBP for the initiation of dialysis under the consideration of the risk of strict control of blood pressure.
Conflict of Interest Statement: none declared
Funding: Japan Society for the Promotion of Science