Predialysis serum lactate levels could predict dialysis withdrawal in Type 1 cardiorenal syndrome patients

Abstract

Background: Renal replacement therapy (RRT) is an effective rescue therapy for Type 1 cardiorenal syndrome (CRS). Previous studies have demonstrated that type 1 CRS patients with severe renal dysfunction were susceptible to sepsis, and that serum lactate has been correlated with the risk of mortality in patients with sepsis. However, the association between serum lactate level and the prognosis of type 1 CRS patients requiring RRT is unknown.

Methods: An inception cohort of 500 type 1 CRS patients who received RRT in a tertiary-care referral hospital in Taiwan from August 2011 to January 2018 were enrolled. The outcomes of interest were dialysis withdrawal and 90-day mortality. The results were further externally validated using sampling data of type 1 CRS patients requiring dialysis from multiple tertiary-care centers.

Findings: The 90-day mortality rate was 52.8% and the incidence rate of dialysis withdrawal was 34.8%. Lower pre-dialysis lactate was correlated with a higher rate of dialysis withdrawal and lower rate of mortality. Generalized additive model showed that 4.2 mmol/L was an adequate cut-off value of lactate to predict mortality. Taking mortality as a competing risk, Fine-Gray subdistribution hazard analysis further indicated that a low lactate level (≦ 4.2 mmol/L) was an independent predictor for the possibility of dialysis withdrawal, as also shown in external validation. The interaction of quick Sequential Organ Failure Assessment score and lactate was associated with dialysis dependence in a disease severity-dependent manner. Furthermore, the associations between hyperlactatemia and dialysis dependence were consistent in the patients with and without sepsis.

Interpretation: Serum lactate level is accurate and capable of forecasting the prognosis along with qSOFA severity for clinical decision-making for treating type 1 CRS patients. Further studies are needed to validate our results.

Funding: This study was supported by grants from Taiwan National Science Council [104-2314-B-002-125-MY3,106-2314-B-002-166-MY3,107-2314-B-002-026-MY3], National Taiwan University Hospital [106-FTN20,106-P02,UN106-014,106-S3582,107-S3809,107-T02,PC1246,VN109-09,109-S4634,UN109-041], Ministry of Science and Technology of the Republic of China [MOST106-2321-B-182-002,106-2314-B-182A-064,MOST107-2321-B-182-004,MOST107-2314-B-182A-138, MOST108-2321-B-182-003,MOST109-2321-B-182-001, MOST108-2314-B-182A-027], Chang Gung Memorial Hospital [CMRPG-2G0361,CMRPG-2H0161,CMRPG-2J0261, CMRPG-2K0091], and Ministry of Health and Welfare of the Republic of China [PMRPG-2L0011].

Keywords: Prognosis; Type 1 cardiorenal syndrome; renal replacement therapy; serum lactate; withdrawal.

Figure 1

Generalized additive model plot for the probability of 90-day mortality against serum lactate levels at the initiation of dialysis. The generalized additive model plot was incorporated with subject-specific random effects expressed as the logarithm of the odds (logit). The probability of outcome events was constructed with lactate levels averaging zero over the range of the data, i.e. lactate = 4.24 ng/mL. Abbreviations: AKI, acute kidney injury; ICU, intensive care unit; qSOFA, quick Sequential Organ Failure Assessment. ^¶Pre-dialysis lactate level ≦ 4.2 mmol/L was defined as low lactate. Pre-dialysis lactate level > 4.2 mmol/L was defined as high lactate.

Figure 2

Cox proportional hazard plots stratified by pre-dialysis serum lactate level for assessing the probability of mortality. All relevant covariates, including characteristics, comorbidities and laboratory data at ICU admission, etiology of AKI, indication for dialysis, dialysis modality, qSOFA score, and plasma lactate level at dialysis, and some of their interactions including those listed in Table 1 were put on a selected variable list to predict the outcome of interest. Cumulative hazard for mortality rates differed significantly for patients with a high lactate level (lactate level > 4.2 mmol/L) and those with a low lactate level (lactate level ≦ 4.2 mmol/L) before dialysis (Log-rank P < 0.001).

Figure 3

Cox proportional hazard plots stratified by pre-dialysis serum lactate level for assessing probability of dialysis withdrawal, taking mortality as a competing risk^¶. All relevant covariates, including characteristics, comorbidities and laboratory data at ICU admission, etiology of AKI, indication for dialysis, dialysis modality, qSOFA score, and plasma lactate level at dialysis, and some of their interactions including those listed in Table 1 were put on a selected variable list to predict the outcome of interest. Cumulative subhazard for dialysis withdrawal differed significantly for patients with a high lactate level (lactate level > 4.2 mmol/L) and those with a low lactate level (lactate level ≦ 4.2 mmol/L) before dialysis (P < 0.001). ^¶Pre-dialysis lactate level ≦ 4.2 mmol/L was defined as low lactate Pre-dialysis lactate level > 4.2 mmol/L was defined as high lactate.

Figure 4

Marginal effects of the interaction between probability of dialysis withdrawal and predialysis qSOFA score according to a high (> 4.2 mmol/L) or low (≦ 4.2 mmol/L) predialysis serum lactate level. The crossed blue and red lines supported that there was an interaction effect, in which an impressive interaction between the probability of dialysis withdrawal and predialysis qSOFA score was confirmed under the influence of a high and low lactate level. The graph showed that the probability of dialysis withdrawal was significantly higher for the acute dialysis patients with a pre-dialysis serum lactate level ≦ 4.2 mmol/L (P < 0.001).

Figure 5

Forest plot depicting subgroup analysis of dialysis withdrawal compared with high and low pre-dialysis serum levels of lactate, taking mortality as a competing risk^¶. The association between low lactate level and a lower risk of dialysis dependence remained consistent across diabetes, sepsis, fluid overload and uremia subgroups as the indication for initiating dialysis (P > 0.05), while this association was more significant in the patients with hypertension (P = 0.001) and without coronary artery disease (P < 0.001), severe congestive HF (NYHA functional class 2–4) (P < 0.001), history of PTCA (P = 0.001) or elective surgery (P < 0.001). Abbreviations: CAD, coronary artery disease; PTCA, percutaneous transluminal coronary angioplasty; ^¶ Pre-dialysis lactate level ≦ 4.2 mmol/L was defined as low lactate Pre-dialysis lactate level > 4.2 mmol/L was defined as high lactate *Congestive heart failure NYHA functional class ≥ 2.