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