Renal impairment increases morbidity and mortality, and as it is a predictor of cardiovascular disease, if detected early, it's preventable and treatable (22). Renal impairment in the elderly is not well studied in Palestine and the region. A recent study in PHC revealed that 23.6% of diabetic patients have renal impairment, (23) while an older survey of patients with hypertension and diabetes in hospitals found that 35.5% have renal impairment (24). The prevalence of renal impairment among Palestinian elderly people was found to be 30%, one of the highest when compared to the global prevalence, which was as follows: 40% in the USA (4), 25.7% in Italy (25), 21.4% in Brazil (5), and 11.4% in China (26). Healthcare providers and policymakers should pay more attention to this to adopt strategies to aid in the early detection of renal impairment to prevent and control it in its early stages, thereby reducing healthcare costs.
It's known that the risk factors of renal impairment are complicated and multifactorial. Consistent with previous studies, multivariate logistic regression reveals that female gender, increased age, polypharmacy, and the presence of a stroke are significantly associated with impaired renal function. Our results showed that females are 2.6 times more likely to have renal impairment than males, which is consistent with previous literature (6, 7, 17). This could be due to the differences in pathophysiology between males and females.
Increased age significantly affects renal impairment, particularly in the elderly above 70. Patients over 80 years old were found to be four times more likely to have renal impairment compared to younger age groups. Increasing age is responsible for some of the pathophysiology of renal impairment where degeneration of sodium content, endothelial function, and renin-angiotensin system happened (25). This could be due to multiple chronic diseases, especially hypertension and diabetes mellitus associated with aging, leading to decreased renal function. This finding should raise the awareness of PHC physicians treating those age groups about the risks of renal impairment, the importance of closely monitoring their kidney function to detect and treat any impairment early, and the importance of controlling chronic diseases that affect renal function.
Polypharmacy, identified as a significant risk factor for potentially inappropriate medication(27), has also been linked to renal impairment in the elderly; the likelihood of renal impairment increases as the number of prescribed medications increases. Our results showed that elderly people with excessive polypharmacy (more than ten medications) are six times more likely to have renal impairment compared to elderly with less than five medications. This is consistent with the literature, which shows that polypharmacy exposure is significantly associated with an increased risk of kidney dysfunction (7, 28, 29). Knowing that pharmacokinetic changes happen with aging, where renal elimination decreases, increases the risk of pharmaceutical ingredient and metabolite accumulation, which in this case increases the risk of renal impairment (9). Polypharmacy raises the risk of adverse drug events, drug-drug interactions, and drug-disease interactions, which increase the risk of renal impairment (16). These findings highlight the importance of implementing strategies to reduce polypharmacy risk factors in the elderly, such as having a single source for medication prescriptions, managing frequent PHC clinic visits, and reducing unnecessary prescriptions by physicians.
Among the chronic diseases reported in our elderly patients, stroke showed a significant association with renal impairment; elderly patients with stroke were 2.5 times more likely to have renal impairment. It's important to note that this is a two-way relationship: while renal impairment is thought to be a predictor of poor clinical outcomes and mortality after stroke, stroke has been found to increase the risk of renal impairment (30, 31). This could be because stroke patients have poorer general health and less controlled chronic diseases and thus are predisposed to develop renal impairment (32). This brings us back to the importance of early detection, treatment, and close monitoring of chronic diseases in the elderly, particularly those known to impair renal function, such as hypertension and diabetes. Patients who have had a stroke require close monitoring of their renal function.
More than one-third of study participants with renal impairment had at least one PIM, with long-acting sulfonylurea being the most common (20.4%). Sulfonylureas, in general, may cause prolonged hypoglycemia, which can be fatal in the elderly (19). In addition, in patients with renal impairment, this medication's side effects increased as their renal clearance decreased, resulting in more hypoglycemic episodes and potentially fatal consequences (21). On the other hand, it was found that some patients with renal impairment used nonsteroidal anti-inflammatory medications, despite the fact that NSAIDs are known for their nephrotoxic effect by reducing renal flow, causing prerenal failure and acute tubulointerstitial nephritis; this should raise physicians' awareness to look for a non-nephrotoxic alternative for pain management in this group (9).
Metformin is known to induce lactic acidosis, especially in patients with impaired renal function, and the recommendation is to closely monitor renal function and adjust the dose or discontinue accordingly (9, 21). However, 3.9% of study participants with renal impairment were on metformin while their GFR was less than 30, and 35.4% were in inappropriate doses according to their GFR level. This emphasizes the importance of assessing renal function before starting metformin, closely monitoring it, and adjusting the dose accordingly. In addition, some of the study's participants were on a combination of ACEI and ARBs, while others were on medications to be used with caution, including medications that need close monitoring to avoid renal function deterioration and electrolyte disturbance and need a dose adjustment. More than half of the study's participants with renal impairment were on RAAS, less than 10% were on spironolactone, and a minority were on a combination of ACEI and spironolactone; those mentioned medications need close monitoring of serum potassium and renal function, as they may lead to hyperkalemia in renal impairment patients, which may be lethal by causing cardiac arrhythmias. Moreover, 4% were on a combination of both loop diuretics with thiazide, which is known to increase the risk of both hyponatremia and hypokalemia, wherefore need close monitoring of serum electrolytes (33, 34).
Study strength and limitations
To our knowledge, this is one of the few studies to report the association between polypharmacy and renal impairment among PHC patients and the first one to study nephrotoxic drugs in renal impairment patients in Palestine. One of the study's limitations was that some important risk factors, such as smoking history, BMI, family history of CKD, and others, were not collected. The second was that psychiatric medications could not be assessed, despite many being considered PIM in patients with renal impairment. Finally, a single eGFR estimation was used, even though at least two readings 90 days apart are required to accurately consider chronic kidney disease diagnosis.