Prevalence of comorbidities, polypharmacy and drug related problems among hospitalized patients with chronic kidney disease

Discussion

This study reveals older patients are more likely increasing in renal failure stage. The progression of CKD rises dramatically with age as supported by the significant finding of ordinal-ordinal correlation by suing Kendall rank correlation coefficient test. The kidneys are affected by the aging process which results in numerous effects on the renal system [10]. The majority of the current participants were male compared females. This is consistence with a previous study that revealed the incidence rate to end stage kidney disease (ESKD) in[MOU20]  Libya was higher in males than females [11] predicting that renal impairment in female start in older age compared with male. The majority of patients were from stage V. The reasons for this finding could be related to that most of the participants live in the South Libya areas and may have a history of many medical conditions and came to hospital after developing ESRD. This is slightly lower than the finding obtained in Ethiopia [12]. The high prevalence rate of ESKD might associated with a limited access to renal transplantation in the Libya [11]. All the patients with CKD have at least one comorbidity. Evidence showed that people with CKD have high mean number of comorbidities than people without CKD [13]. Majority of the patients of this study have anemia similar to Ethiopia patients [12]. However, in Nigeria’s study, only few patients had anemia [14]. Reasons for this difference could be explained that patients were in stage IV and V renal failure. In advanced stages of CKD, anemia is existing in high number of patients [15, 16]. Appropriate and timely intervention using erthyropoiesis-stimulating agent is needed to improve clinical indices and to retard the progression of renal failure [17]. Interestingly, there was no prescribing of erythropoietin for our patients. The absence of erythropoietin-stimulating agents from the treatment regimen might be due to shortage of medication in hospital.

The majority of CKD patients have electrolytes imbalance. This trend is higher than the published study conducted in Ethiopia which represented the electrolyte abnormality prevalence was among CKD inpatients, the most serious electrolyte disturbances involve abnormalities in the levels of sodium, potassium or calcium. Hyponatremia is highly prevalent in patients with CKD [18]. The majority of the patients have hyponatremia represented highest rate of electrolyte imbalances. Hypernatremia is much less common than Hyponatremia among patients admitted to the hospital and 10.0% in critical care unit [19]. This trend is in consistence with present findings, since most of the patients in advanced stages of CKD. It has been documented that the intestinal[MOU20]  calcium absorption was decreased [20]. Reduced production of active vitamin D will result in reduced absorption of calcium from the gut [21]. Hypocalcemia was observed in patients of this study as the eGFR falls, the renal excretion of potassium is reduced and prevalence of hyperkalemia increases from 02.0% in patients with eGFR > 60 ml/min/1.73 m² to 42% in patients with eGFR < 20 ml/min/1.73 m² [22, 23]. Patients with CKD may be predisposed to hyperkalemia for a variety of reasons. Interestingly, hypokalemia was higher in current study than hyperkalemia.

Hypertension and diabetes mellitus are the most common comorbid conditions present in CKD while those have these two comorbidities are almost half of the patients. Published data indicated that patients with diabetes mellitus and hypertension have seven-fold greater risk for progression to end-stage renal failure [24]. When CKD and hypertension exist together, the risk of CVD morbidity and mortality are substantially increased [25, 26]. Patients presenting with CKD are particularly vulnerable to infections as the quality of their humoral and cellular immune response is impaired [27] and overwhelming uremia, which is associated with alterations in primary host defense mechanisms [28]. In current study, half of the patients have bacterial infection while[MOU21]  about double of patients have prescribed antibiotics during staying in hospital. Basically, medical professionals believe patient has an infection based on their symptoms, physical examination, laboratory results and risk factors. However, at SMC, the poor and incomplete documenting practice among physicians was noticed in patients' records about infection, the measurement used for diagnosing bacterial infections and frequent missing antibiotic prescribing for it. Bone abnormalities are found in the majority of patients with CKD stages III - V [29]. About half of patients have chronic renal disease - mineral and bone disorder. Numerous cohort studies have shown association between disorders of mineral metabolism or deranged markers of CKD-MBD and poor clinical outcomes as fracture, cardiovascular disease and mortality in patients with CKD [30 - 32]. Dyslipidemia is often present in patients with renal failure, long before they reach ESRD [33, 34]. Out of total, about third of the patients have been given statins, only eight patients have dyslipidemia. This shows that the majority of patients who treated by statins have successful management of their dyslipidemia. Patients with CKD suffer from high comorbidities. In German CKD cohort, the prevalence of polypharmacy was 81.8%, which was increased with the increase of CKD stages [35]. Polypharmacy was observed among all the patients and the majority of patients using more than 10 medications. Additionally, it is noticed a substantial correlation between rising drug usage per patient and deteriorating renal function. The interpretation of the rising drug use may point to increase comorbidities among renal patients, which contributes to advancement of renal impediments in stages [36]. Polypharmacy has the potential to DRPs. Australian general practices found that the mean number of medications prescribed to people with CKD was 8.2 with third of the patients prescribed at least one potentially inappropriate medication [37]. Currently, almost all the patients have at least one DRPs. Inappropriate polypharmacy can lead to significant morbidities and mortality [38]. Of total medication orders for CKD patients, supplements were the highest category of drugs which was prescribed during patients staying in hospital. Dietary prescription may limit foods which are high in vitamins, particularly water-soluble vitamins, because of their high potassium or phosphorus content [39]. The majority of patients have anemia and nearly half of the cases have mineral and bone disorder who need supplements to correct these deficiencies. The second major drugs prescribed for CKD patients was anti-hypertension. Blood pressure becomes more difficult to control with advancing CKD stages [40]. ACEIs were more prescribed orders compared with calcium channel blockers [28]. The effects of antihypertensive therapy on kidney function need to be carefully considered. According to the current KDIGO guideline [1] that recommends RAAS blockade as the first-line therapy in non-diabetic and proteinuric patients with CKD. RAAS inhibitor therapy compared with CCBs may provide kidney some benefits among patients with advanced CKD and cardiovascular protection [41]. However, currently, the percentage of patients prescribed ACEIs and ARBs was less than prescribing CCBs. Infectious diseases are the second leading cause of death in end-stage CKD patients [42]. Thus, antibiotic treatment is common in these patients and requires special attention. All antibiotic use, whether appropriate or not, carries a risk of contributing to the development of antibiotic resistance. High antibiotic use is unnecessary or inappropriate. Patients have infection while double of patients have prescribed antibiotics without documented their indications in medical records[MOU22] [ma23] . Appropriateness of antibiotic use determined by presence documented indications in medical records. However, this documentation may miss indication data which lead to underestimation the risk of inappropriate antibiotic use.

Evidence indicates that as CKD progresses and medication usage increases, the prevalence of DRPs increases [43]. A significant relationship between stages of CKD and the prevalence of DRPs was found. In the same way, the result shows a significant relationship between rate of comorbidities and DRPs. So, DRPs were reported among patients with stage V and just over the quarter accounted with those having stage IV. But, polypharmacy has insignificant relationship with prevalence DRPs. This finding has a lower rate compared with Indonesian study that the average of DRPs about ten DRPs for each patient [44]. In contrast, higher than similar study was conducted in Ethiopia which reported the average of DRPs was 1.9 per patient [12]. This variation could relate to differences in the characteristics the population and duration of study. Nearly, two thirds of patients with CKD stage V patients are likely to have multiple comorbidities and complications and their treatment need a variety of drugs which are potential risk of DRPs [45]. The poor collaboration between physicians and pharmacists was recognized as a significant factor responsible for an inappropriate prescription [46]. DRPs data analysis showed the most common type of DRPs was need additional drug therapy or untreated conditions. This explained by the high burden of comorbidities among the study population and higher rate of untreated condition could be illustrated that physicians are more likely focusing on major conditions and paying less attention on minor disease conditions as anemia. Physician prescribing errors can arise from the choice of the wrong drug or improper drug selection. Thus, about 15.0% of the prescribed drugs were under improper drug selection. It is worth noting that anti-diabetic drugs (metformin) is prescribed to nine patients which is the most common contraindicated used medicines in CKD patients because it may cause life-threatening lactic acidosis [47]. However, the use of metformin in patients with mild renal impairment was subject to debate. The poor quality of data about prescribing decisions in medical notes have been identified as contributing to prescribing errors [48]. Medication indications are not routinely documented by prescribers, in inpatient and outpatient settings [49]. Currently, drug use without indication were reported by 13.5% of patients and 84.1% of patients have received antibiotics, 50.0% of have recoded for infection indication. In line with treatment guidelines and recommendations, only patients who have confirmed infectious diagnosis are expected to be given an antibiotic prescription [50, 51].  

One of the most important DRPs in patients with renal impairment is medication dosing errors. Hence, many medications require dosage adjustments in CKD in order to ensure efficacy and prevent toxicity. Currently, 12.5% prescribed drugs have over-therapeutic dose of all DRPs identified. As, metoclopramide need adjusting dose according to patient GFR as a similar trend in Ethiopia and Canada [12, 52]. Unnecessary decreases in dosage may result in under-treatment, or changing to an alternate drug with a narrower therapeutic index, lower efficacy or both. A major reason for inappropriate dosage adjustment is the underestimation of potential adverse consequences [53]. One of the strategies were suggested to assist practitioners in monitoring and adjusting drug therapy in patients is clinical pharmacist dosing services [54]. CKD is a major health burden that amplifies the risk for adverse events [55], the mild interaction experienced by renal competent patients may be life threatening in patients with impaired renal disease since their pharmacokinetic responses to the drugs are altered [56]. The potential drug-drug interactions was reported for few patients of all the prescribed drugs. A similar trend was reported in Ethiopia for of DRPs [12]. Early diagnosis, optimal use of medications, treatment of comorbid conditions which they have all been associated with better outcomes in patients with CKD [29]. Given the nature of clinical pharmacist major responsibilities and tasks, they can directly be engaged[MOU24]  in the care of CKD and ESRD patients in different settings by identifying and addressing the DRPs in hospitals, introduce their recommendations regarding prevention and treatment of these problems and collaboration between all healthcare providers [57]. Clinical pharmacist-led programs showed higher proportions of CKD patients achieving hemoglobin target [58] increased medication knowledge [59] decreased hospitalization rate [28] and an overall improvement in the quality of life of CKD patient [60]. Based on the above, enhancing the involvement of clinical pharmacist may be one potential strategy to improvement patient healthcare outcome.

Conclusion: The majority of the CKD patients in Libya are middle-aged with advanced stages. High rate of Libyan patients have comorbidities and polypharmacy with DRPs. To lower the incidence rate of DRPs among CKD patients, therapeutic intervention is necessary. Since their intervention involve patient follow-up, medication review and dose adjustments according to the functions of the kidneys, the clinical pharmacist's presence at hospital is a crucial for enhancing the care of CKD patients. To achieve this goal, physician and clinical pharmacist in the renal field must improve their communication, collaboration and teamwork.