Discussion.
The present study suggests the relationship between high NLR and PLR
with all-cause mortality in patients with CKD. Thus, those patients who
had a high NLR or PLR showed twice the risk of dying compared to those
who had these ratios within normal limits. Our results are similar to a
study conducted in 350 Japanese patients with CKD in stages 1 to 4, in
which a high NLR was associated with a higher probability of requiring
dialysis and death(15). Likewise, they are similar to a study done in
165 Turkish patients with CKD in stages 1 to 3 that found that a high
NLR was associated with higher mortality from all causes(21). In
contrast, Chinese patients with CKD in stages 1 to 4, did not find an
association between NLR and cardiovascular mortality or of any
cause(20). Methodological differences can explain these discrepancies.
Although the study included a more significant number of patients (938)
and was multicenter, it also had a smaller number of diabetic patients
(23.8%) compared to the Japanese (37%), Turkish (41.4%) or in our
study (30%), and could explain these differences, due to the higher
mortality in diabetic patients(28). Similarly, the mean age of the
Chinese patients was comparatively lower (52.8) than that of the
patients in the Japanese (68), Turkish (73.8) and our studies (78.3),
which is essential because older age is associated with higher mortality
in CKD(29).
The association of NLR and survival is justified in that is a marker of
inflammation that predicts complications and mortality in patients with
chronic diseases. This biomarker indicates an imbalance between effector
cells (neutrophils), which reflect oxidative stress and regulatory cells
(lymphocytes), which decrease the pro-inflammatory state(30). This
relationship between neutrophil count and lymphocyte count is a new
measure of inflammation in different diseases with systemic inflammation
such as CKD(31) Uncontrolled inflammation causes glomerular, tubular and
interstitial damage that leads to renal hemodynamic imbalance and
failure to control blood pressure(30).
Regarding PLR and mortality, we have similar findings to a study in
patients with rapidly progressive glomerulonephritis in which both NLR
and PRL were associated with mortality(32). However, a Turkish study no
found association between PRL and mortality or the need of dialysis,
but, the PRL group that died was a mean of 112 ± 267, while in our study
a high PLR was considered as cut-off > 232.5(21). In that
sense, another study found that relationship between PRL and mortality
is not a linear relationship and that it can follow a curve in J-shaped
that differs according to ethnicity (PLR≥83.18) and albumin (PLR ≥
113.89)(42). It is likely that, as with NLR, systemic inflammation may
play a fundamental role. Increase in platelets or an increase in
lymphocytes is typical to find in patients with inflammatory states(33).
Platelet release can be modulated by inflammatory cytokines as a
mechanism for rapid recovery, while decreased lymphocytes may be due to
increased lymphocyte apoptosis and suppressed lymphocyte production
caused by high levels of cortisol in response to inflammation(33,34).
Although the association between NLR, PLR and mortality may be related
to more significant inflammation, it would also be mediated by CKD
progression, because in the advanced stages of the disease, there is
higher mortality (34). However, after sensitivity analysis, removing
stage 4 and 5 participants, lymphocyte ratios remained as an independent
risk marker for mortality. This finding could suppose other additional
routes to the progression of the disease to explain this association in
our population. Moreover, several studies reported NLR and PLR
associated with albuminuria (regardless of GFR) and decrease in
GFR.(19,35). So, this finding becomes relevant due to the association
between albuminuria, CKD progression, and mortality(32,33).
Our study has limitations. First, being a retrospective study, the data
obtained could have deficiencies in its registration. Second, there is
the possible inclusion of patients with subclinical inflammatory and
infectious diseases, which are not registered in the SSCKD or RESULAB
database. Third, no other possible factors that could potentially
influence mortality, such as nutritional status, albuminuria,
cardiovascular disease, obesity, smoking, and acute renal injury, have
been evaluated. Fourth, by the design of our study, we can only assume
that lymphocyte ratios are biomarkers of risk and not of causality.
Finally, the measurement of the ratios has only been carried out at the
beginning of the follow-up; therefore, we not evaluated variations in
time and influence in the mortality.
In conclusion, our study suggests the relationship between high NLR and
PLR with all-cause mortality in patients with CKD. The patients who had
a high NLR or PLR showed twice the risk of dying compared to those who
had these ratios within normal limits. These ratios are constructed with
values usually collected in hemograms commonly used for patient
follow-up. Being constructed based on a cheap and common exam and, due
to our results, we believe that it could be considered within the usual
practice in resource countries limited.