Risk of mortality after joint replacement

6. Discussion

6.4 Risk of mortality after joint replacement

In the multivariable Cox regression model, significant differences in mortality in different CKD classes persisted throughout follow-up. This is a new finding.

Previously, Boniello et al. (2018) reported HR of 2.5 in 30-day mortality following TJA in patients with CKD 3-5 when comparing them to patients with CKD 1-2 (Boniello et al., 2018). The results of the present study concur with this finding. Similarly, in 90 days, HR for mortality is estimated at between 2.0 and 3.8 when comparing CKD 3-5

to CKD 1-2 (Bozic et al., 2012a; Bozic et al., 2012b; Hunt et al., 2013). The present study obtained no conflicting results to contradict these studies. In the short term there is one paper describing mortality across all values of eGFR. Warth et al. 2015 showed a curve for continuous odds ratio for 30-day mortality using eGFR as a continuous variable. This curve showed that OR for mortality increases in logarithmic fashion; the higher the eGFR, the lower the mortality. Their model was not adjusted and they did not categorize eGFR into different CKD stages (Warth et al., 2015). The finding in the present study was similar, but in the present study differences in HRs were greater; however, ORs and HRs are not comparable and the present study did not report adjusted OR for different postoperative time intervals. Instead, it reported an HR for the entire follow-up of each patient. In the short term, none of these studies reported survival rates separately in CKD as the present study did.

In joint replacement population, 90-day mortality varies between 0.2 and 0.3% (Hunt et al., 2013; Middleton et al., 2017). Nevertheless, the present study reported 90-day mortality of 0.1%, 0.4%,1.0%, and 1.7% in CKD stages 1, 2, 3 and 4-5 respectively.

Thus, even moderate CKD seemed to increase short-term mortality remarkably.

When CKD (eGFR < 60mL/min/1.73m²) existed alongside with diabetes, the 90-day mortality rate was 3.1%. This was more that could be extracted from the mortality rates of diabetes (0.3%) and CKD (0.8%) alone. The result was similar when looking at mortality rates of diabetes and CKD patients one year postoperatively. In patients with both conditions, diabetic nephropathy most probably underlies CKD and these patients presumably have other diabetic complications as well. This could explain the high mortality in this patient group.

In the long term, only CKD stage 5 patients are so far known to have poor survival (Goffin et al., 2006; Lieu et al., 2014). At a median follow up time of 4.2 years, Jämsen et al. (2013) reported HR of 1.74 (insignificant), 1.6 (insignificant) 5.04 (significant) for

there was no difference in AKI rates when comparing cemented, hybrid and

cementless prostheses. As there is patient selection between cemented and cementless prostheses, the present study can draw no conclusions on the insignificant results.

Still, patients with advanced age and morbidities (and thus more prone to developing AKI) would probably end up having cemented prostheses, suggesting that there is no major connection between aminoglycoside cement and AKI.

In the RIFLE criteria, the letters L and E stand for loss of renal function for more than four weeks, and end-stage renal dialysis, meaning renal replacement therapy for over three months (Bellomo et al., 2007). In the present cohort, two out of 58 AKI patients received dialysis, but neither of them needed it for over four weeks and thus, were not classified into either of the two categories. Other studies have reported similar findings, Jafari et al. (2010) reported seven out of 98 (7%) AKI patients receiving dialysis while the cohort of Kimmel et al. (2014) had no need for dialysis at all. Thus, it seems that AKI secondarily to joint replacement surgery rarely leads to a need for permanent dialysis. Accordingly, in the literature, after major surgery, only 1% of patients with AKI develop end-stage kidney disease in 1-year follow up (Grams et al., 2016).

6.4 Risk of mortality after joint replacement

In the multivariable Cox regression model, significant differences in mortality in different CKD classes persisted throughout follow-up. This is a new finding.

Thus, even moderate CKD seemed to increase short-term mortality remarkably.

mortality in CKD stages 2, 3 and 4-5 respectively compared to CKD stage 1. They had 1,998 patients, all of whom were older than 75 years of age (Jämsen et al., 2013b).

The present study reported much higher HR for mortality in CKD stages 4-5 (HR 8.1;

95% CI 6.3-10.3). The different age structure of the patients probably explains this difference. Probably due to lack of statistical power, they had no significant finding for CKD stages 2 and 3 in adjusted analysis. Deegan et al. 2014 showed a significant HR of 2 when comparing CKD 1-2 to CKD 3 (Deegan et al., 2014). This finding concurs with the present study, although the groups were different. The present study was the first to show that long-term mortality increases with every step up in the CKD classification. Even mild CKD was associated with increased mortality.

In the multivariable model, CKD was greatest explanator of mortality (HRs 1.9; 3.8;

and 8.1 in CKD 2, 3 and 4-5 respectively), when comparing to hypertension (HR 1.4), CHF (HR 2.1), coronary artery disease (HR 1.5) or diabetes (HR 1.7). Previously, in two separate articles, Bozic et al. in 2012 reported that HR for 90-day mortality was higher in CKDpatients (2.0-2.2) than in diabetes patients (1.3-1.2), while in CHF, HR was of the same magnitude (2,1-2,2). They found no significant results concerning hypertension or ischemic heart disease (Bozic et al., 2012a; Bozic et al., 2012). Hunt et al. 2013 also reported 90-day mortality to be higher when comparing CKD (HR 2,2) and diabetes without or with complications (HRs 1.1 and 2.0). In their model,

however, CHF was a greater explanator of mortality (HR 2,6) (Hunt et al., 2013). The present study compared CKD groups 2, 3 and 4-5 to group 1, while the two

previously mentioned studies compared non-CKD (CKD stage 1-2) to CKD (CKD stage 3-5) patients. These two studies also did not provide any demographic data. This makes the results hard to compare with each other. However, the results of the present study highlight that CKD should most definitely be taken into account when evaluating an individual patient´s comorbidities postoperatively. However, the study does not answer the question “why is CKD such a strong predictor of mortality in this

population?” One possible explanation could be that CKD is usually a manifestation of long-term diabetes or hypertension (Levey, Andrew S. et al., 2003). Similar to the present study, in a univariable analysis of a single multiethnic cohort, CKD (HR 3.4) was a stronger predictor of death than was diabetes (HR 1.3), hypertension (HR 2.1) or ischemic heart disease (HR 2.8) (Jesky et al., 2013).

The present study was the first to investigate risk of mortality in different

combinations of comorbid diseases and CKD in a joint replacement population. As noted earlier, diabetes had synergistic effects with CKD in 90-day and 1-year mortality rates. After that, at five years, the effect of this combination was only additional. The synergistic effect could be explained by diabetes causing patients more morbidity burden contributing to in many different health problems such as cardiovascular diseases, neuropathies, but also diabetic nephropathy. Diabetes combined with CKD reportedly increases mortality more than sum of their individual effects (Afkarian et al., 2013). When CKD coexisted with hypertension, CHF or cardiovascular diseases, an increased risk was seen. This risk was nevertheless additive as two diseases produced a risk that equals the sum of the risks of individual diseases.

As a conclusion, CKD constitutes a significant risk for death that is undoubtedly comparable to other previously known risk factors. Even mild forms of CKD predispose patients to increased risk of death. As more than half of patients have CKD 2 and 10% have CKD 3, this is important information that these patients have less time to enjoy the improved mobility and pain relief that joint replacement offers.

However, in the cohort, at five years, 94% of CKD 1 patients and 90% of CKD 2 patients were still alive. Thus, patients with CKD 1-2 most likely benefit from their operation to a great extent, whereas patients with CKD 4-5 have poor survival; only 53% of the patients were alive at five years. In these patients proceeding to joint replacement should be carefully considered as the operation would produce only few

mortality in CKD stages 2, 3 and 4-5 respectively compared to CKD stage 1. They had 1,998 patients, all of whom were older than 75 years of age (Jämsen et al., 2013b).

The present study reported much higher HR for mortality in CKD stages 4-5 (HR 8.1;

In the multivariable model, CKD was greatest explanator of mortality (HRs 1.9; 3.8;

however, CHF was a greater explanator of mortality (HR 2,6) (Hunt et al., 2013). The present study compared CKD groups 2, 3 and 4-5 to group 1, while the two

The present study was the first to investigate risk of mortality in different

improved life years, especially when treating slowly developing knee arthritis.

However, when a patient suffers from painful osteonecrosis of the femoral head, operation is usually indicated even given the poor renal function. As rehabilitation takes several weeks (Hamel et al., 2008) and life expectancy is limited, patients gain less quality adjusted life years. In this patient group, risk of death should be recognized and discussed preoperatively, and other treatment methods such as analgesics and enhanced physiotherapy should be considered as alternative treatment methods to surgery. Patients with CKD stage 3 had slightly reduced but still fairly good survival;

79% at five years. However, when non-CKD patients were compared to CKD

patients, a combination of CKD with other comorbidities led to poorer survival at five years. In patients with a combination of CKD and diabetes, survival was 69% at five years and 67% among patients with CKD and CHF. In patients with both CKD and coronary disease, 72% were still alive five years postoperatively. Thus, patients with CKD stage 3, and especially patients with a combination of CKD and diabetes, coronary disease or CHF, have a significantly higher risk for mortality and this should guide clinicians in decision-making, especially if the indication for surgery is borderline between whether to operate or not. In developed countries, healthcare budgets are vast but not limitless. Limited healthcare funds should be allocated to interventions that produce the most quality adjusted life years rather than to those interventions that donot. However, whether QALYs in joint replacement surgery differ in different CKD stages, is unknown and needs research in the future.

As preoperative CKD was strongly related to postoperative deaths, so was

postoperative AKI. AKI patients had poor survival compared to non-AKI patients.

However, in the cohort, it is not known whether postoperative AKI itself,

characteristics of AKI patients, or possibly both, contributed to high postoperative mortality. This issue also warrants future research. Similar to the present study, in hip replacement patients, postoperative AKI is known to increase in-hospital mortality

8-85

fold (Singh & Cleveland, 2020). In a series of 425 patients (with 67 AKI cases), no deaths were recorded at three-month follow-up (Kimmel et al., 2014). Other studies on postoperative AKI after joint replacement have not reported mortality (Ferguson et al., 2017; Jafari et al., 2010; Nowicka & Selvaraj, 2016; Perregaard et al., 2016).

In document Chronic Kidney Disease in Patients Undergoing Hip or Knee Joint Replacement (sivua 82-86)