Globally there is a huge rise in the incidence of treated End Stage Renal Disease (ESRD) which urges us to pay attention to this devastating social, economic, and health problem. The annual mortality rate remains stubbornly high in ESRD patients and awareness of ESRD remains limited in developing countries. Most individuals with ESRD in developing countries go undetected at early stages. So, it comes out to be a critical health issue of developing countries like Pakistan. While recommendations on ESRD progression are generally based on data from developed nations and may not necessarily apply to settings of low-resource developing countries, the strength of this study lies in the fact that it is a first cohort study to investigate the joint prognostic influence of covariates for dialysis patients in the respective population of low-resource settings. In this study, we inspected the joint prognostic influence of demographic and biochemical variables, to ascertain the prognostic information for best and worst survival of dialysis receiving patients.
In our study, dialysis duration (months) (p-value:0.027), inter-dialytic weight gain (p-value: 0.001), serum potassium (p-value: <0.001), serum hemoglobin (p-value: <0.001), and serum albumin (p-value: <0.001) appeared as significant prognostic factors. These are clinically adjustable prognostic factors where increased dialysis duration time reflects a lower risk of death in dialysis patients. These reduced chances of death over the course of time can be explained by the stability of clinical variables attributed to dialysis. Moreover, it may be because most patients opt for dialysis at a very late stage. The maximum number of deaths in the initial period can be due to worse clinical conditions at the time of presentation, thereby decreasing the chances of death by stabilizing clinical variables over time. Studies concerning the duration of dialysis of patients lead to conflicting conclusions. Contrary to our findings, some studies found no significant relationship of dialysis duration on the survival and quality of life of patients (Barzegar et al. 2017; Parvan et al. 2012; A. L-Jumaih et al. 2011). Gerasimoula et al. (2015), Anees et al. (2011), and Taheri et al. (2013) reported that increased duration of disease by combining supplementary diseases and aging could negatively impact patients’ quality of life. Inconsistent with the aforementioned studies, Guerra et al. (2012) and Santos et al. (2007) compared hemodialysis patient’s mental function scores for less and more than 3 years, and it was believed that elapsed onset of hemodialysis might increase the patient’s adaptation to hemodialysis and by improving the uremic symptoms can enhance their performance, similar to the results which we observed (Morsch et al. 2006). The dissimilarities between these studies likely underscore the different social and health support systems in different countries.
Zhang et al. (2019) reported hypoalbuminemia was associated with a worse renal prognosis in dialysis patients with type 2 diabetes mellitus and diabetic nephropathy. Lang et al. (2018) found low serum albumin levels were associated with declined kidney function. Whereas contradictory conclusion had been made by Alves et al. (2018) that mortality risk increased in ESRD patients with low serum albumin and high C-reactive protein (CRP), but it was not observed the same, with low serum albumin and normal CRP. Minatoguchi et al. (2018) reported hypoalbuminemia as a strong predictor of infection-related in-hospital death and for poor prognosis of hemodialysis patients. Gama-Axelsson et al. (2012) stated that low serum albumin levels are found to be strongly associated with inflammation in dialysis patients. Naves et al. (2011) reported that low levels of serum albumin are associated with an increased mortality rate. Iseki et al. (1993) identified serum albumin as a strong predictor of mortality among chronic hemodialysis patients and suggested that the low level of serum albumin should be cautiously treated, confirming our current findings.
Our findings confirmed the several past investigations which found increased Inter-dialytic weight gain (IDWG) harmful for the survival of CKD patients. Kalantar-Zadeh et al. (2009) concluded that higher Inter-dialytic weight gain (IDWG) proved to be related to a higher risk of death. Lopez et al. (2005) concluded that higher pre-dialysis IDWG had negative aspects, albeit the beneficial impact of IDWG upon nutritional status has the better long-term prognosis of patients. Rodriguez et al. (2005) reported that an IDWG less than 1.5 to 2.0 kg was the most favorable target for the survival of patients. Kimmel et al. (2000) had also observed a similar type of relationship, observing the increase in IDWG was associated with a high risk of mortality.
Pirklbauer, M. (2020) discussed hypokalemia and hyperkalemia that severe hyperkalemia can cause electrocardiogram abnormalities, muscle weakness, and ascending paralysis, in line with the findings of Abuelo (2018) and An et al. (2012), contrariwise reported that hypokalemia was not associated with all-cause mortality. Karaboyas et al. (2017) reported a higher level of serum_potassium (serum_k) associated with worse survival and related outcomes. In prior studies, similar results were drawn about Hyperkalemia that requires intent monitoring. Kovesdy et al. (2007) and Bleyer et al. (2006) examined the association between pre-dialysis serum_k levels and mortality. Pre-dialysis serum_k between recommended range 4.6 to 5.3 mEq/L was reported to be associated with the higher survival of patients, while serum_k < 4.0 or > 5.6 mEq/L resulted in association with increased mortality, consistent with our study findings.
Karaboyas et al. (2020) reported that hemodialysis commencement with anemia was observed to be associated with increased mortality risk. Management of anemia in ESRD patients can improve the survival of these patients on dialysis therapy. By conducting a short-term study Kawamoto et al. (2018) stated that low hemoglobin (Hb) level at the beginning of dialysis did not prove harmful for the short-term prognosis of patients. Mimura et al. (2015) recommended maintaining the target Hb level of dialysis patients reliant on their ages, which offered beneficial survival of patients. Gilbertson et al. (2008) verified that a longer time duration with a Hb below the target range can be a primary driver of the improved risk of mortality. Regidor et al. (2006) explored associations between stable Hb levels 12 to with the greatest survival and the lower range of the hb (11 to 11.5 g/dl) found to be associated with a higher death risk. Despite of, in previous studies (Locatelli et al., 2004; Collins, 2002; Collins et al., 2000) had examined the associations between baseline hb levels and survival without bothering about the changes in hb levels over time. Ofsthun et al. (2003) established the findings that higher hb level has no association with increased risk of death. Also, Positive link between survival and high Hb level reported by Collins et al. (2001) supported the results of our study.
To study possible interaction effects, it was assessed whether different conditions for a covariate produce variant results, depending on the conditions considered for a second covariate. We have looked forward to the combined effects of covariates, as there is more to consider than simply the marginal effect of each covariate. The lowest hazard ratio (0.0066) explained a 99.34% reduction in hazard risk for the patient who achieved a lower level of IDWG, lower level of serum_k, higher level of Hb, and higher level of serum_alb with less age group. Such a lower hazard risk value of 99.34% would be the best possible condition for the current population under study. The possible worst condition of a patient under dialysis would be with the highest hazard ratio of 6.74 times more hazard risk with higher IDWG, higher serum_k level, lower Hb level, and lower serum_alb level regardless of age. Overall, at a high level of serum_alb and Hb, low level of IDWG, and medium serum_k, all together, with three age groups of patients (low, medium, and high resp.) demonstrated better survival condition and good prognosis for such patients, reducing hazard risk by (99.34%, 99.09%, 98.80% resp). Overall, it has been observed that shift towards high levels of serum_alb and Hb within the recommended range of IDWG and serum_k, all together, irrespective of the age of the patient (low, medium, and high resp.) demonstrated better survival condition and good prognosis for such patients.
All international guidelines as well as the European Best Practice Guidelines (EBPG) and the United States Kidney Disease Outcomes Quality Initiative (KDOQI) (2012) advised that individuals should achieve the specific target status of clinical covariates within the mentioned time of being seen by nephrologists. The current study immediately after the initiation of dialysis of ESRF patients demonstrated the worst survival. Since dialysis is itself invasive therapy with its own complications therefore maintenance of significant clinical covariates in recommended target ranges is the main concern for better prognosis of these patients.
This study has a possibility for further research with other medical conditions such as obesity, cigarette smoking measured in pack/years, the daily quantity of alcohol consumption, or prohibited drug consumption which may also ultimately contribute to poor survival. Current data is deficient in these fine details. Secondly, patients’ characteristics in this study can be further discussed in comparison to other studies, those who have a high prevalence of chronic kidney failure patients, such as in liver and cardiovascular diseases.