Underdiagnosed CKD in Geriatric Trauma Patients and Potent Prevention of Renal Impairment from Polypharmacy Risks through Individual Pharmacotherapy Management (IPM-III)

Abstract

The aging global patient population with multimorbidity and concomitant polypharmacy is at increased risk for acute and chronic kidney disease, particularly with severe additional disease states or invasive surgical procedures. Because from the expertise of more than 58,600 self-reviewed medications, adverse drug reactions, drug interactions, inadequate dosing, and contraindications all proved to cause or exacerbate the worsening of renal function, we analyzed the association of an electronic patient record- and Summaries of Product Characteristics (SmPCs)-based comprehensive individual pharmacotherapy management (IPM) in the setting of 14 daily interdisciplinary patient visits with the outcome: further renal impairment with reduction of eGFR ≥ 20 mL/min (redGFR) in hospitalized trauma patients ≥ 70 years of age. The retrospective clinical study of 404 trauma patients comparing the historical control group (CG) before IPM with the IPM intervention group (IG) revealed a group-match in terms of potential confounders such as age, sex, BMI, arterial hypertension, diabetes mellitus, and injury patterns. Preexisting chronic kidney disease (CKD) > stage 2 diagnosed as eGFR < 60 mL/min/1.73 m² on hospital admission was 42% in the CG versus 50% in the IG, although in each group only less than 50% of this was coded as an ICD diagnosis in the patients' discharge letters (19% in CG and 21% in IG). IPM revealed an absolute risk reduction in redGFR of 5.5% (11 of 199 CG patients) to 0% in the IPM visit IG, a relative risk reduction of 100%, NNT 18, indicating high efficacy of IPM and benefit in improving outcomes. There even remained an additive superimposed significant association that included patients in the IPM group before/beyond the 14 daily IPM interventions, with a relative redGFR risk reduction of 0.55 (55%) to 2.5% (5 of 204 patients), OR 0.48 [95% CI 0.438-0.538] (p < 0.001). Bacteriuria, loop diuretics, allopurinol, eGFR ≥ 60 mL/min/1.73 m², eGFR < 60 mL/min/1.73 m², and CKD 3b were significantly associated with redGFR; of the latter, 10.5% developed redGFR. Further multivariable regression analysis adjusting for these and established risk factors revealed an additive, superimposed IPM effect on redGFR with an OR 0.238 [95% CI 0.06-0.91], relative risk reduction of 76.2%, regression coefficient -1.437 including patients not yet visited in the IPM period. As consequences of the IPM procedure, the IG differed from the CG by a significant reduction of NSAIDs (p < 0.001), HCT (p = 0.028) and Würzburger pain drip (p < 0.001), and significantly increased prescription rate of antibiotics (p = 0.004). In conclusion, (1) more than 50% of CKD in geriatric patients was not pre-recognized and underdiagnosed, and (2) the electronic patient records-based IPM interdisciplinary networking strategy was associated with effective prevention of further periinterventional renal impairment and requires obligatory implementation in all elderly patients to urgently improve patient and drug safety.

Keywords: acute kidney injury (AKI); adverse drug reactions (ADRs); chronic kidney disease (CKD); drug safety; drug-drug interactions (DDIs); electronic patient records; geriatric patients; iatrogenic risk; individual pharmacotherapy management; medication review; multimorbidity; overdosage; patient safety; pharmacovigilance; polypharmacy; prevention; socioeconomic healthcare system burden; underdiagnosed.

Figure 1

Comprehensive, reproducible IPM based on the electronic patient record.

Figure 2

Baseline data and diagnoses accounted comparing CG and IG (prevalence percentages, except for age, BMI, and number of medications mean ± SD).

Figure 3

Injury pattern (%) of the lower and upper extremities and others in geriatric patients admitted to the traumatology department, comparing control and intervention group.

Figure 4

Comparing redGFR rate in the CG 11/199 (5.5%) with the IPM-visit IG 0/199, (0%) and trendline. * Due to the 14-day IPM ward rounds interval and blinded recruitment the intervention period group (204 patients) also included 5 patients who manifested redGFR before/outside IPM whereas for the IPM patients in context with the visit redGFR frequency reached zero. * There is an OR of 0.48 [95% CI 0.438–0.538], p < 0.001, already for the intervention group even including all patients with redGFR before/outside IPM. ** For the IG with IPM there was a complete absolute risk reduction by 5.5%, relative risk reduction 100%, NNT 18.

Figure 5

Number of drugs per hospitalized trauma patient comparing CG (11.04 ± 4.8; median 11) and IG (10.45 ± 3.58, median 10) with reference to the periinterventional entire medication list. All initiated despresciption of drugs, which require gradual dose reduction, e.g., antipsychotics, benzodiazepines or alpha blockers, are not reflected here because the perioperative stay in the trauma department was usually short, and thus medication withdrawal was not completed during the follow-up period at UKH.

Figure 6

Prescription rates (%) of drugs and drug groups comparing CG and IG. Gradual discontinuations of, e.g., antipsychotics, benzodiazepines or alpha blockers are not figured here because most often not completed during the short hospital stay. * Combination of tramadol, metamizole, and metoclopramide—intravenously or partially orally.

Figure 7

Measurement of an even potentially superimposed IPM effect. Association of IPM with redGFR including the IG patients presenting redGFR before or outside the IPM visit, p < 0.001.