Renal Insufficiency and Medication in Nursing Home Residents

A cross-sectional study (IMREN)

Background: Nursing home residents often suffer from a multiplicity of medical conditions and take many different drugs. Many drugs are eliminated via the kidneys and thus require dose adjustment in patients with renal insufficiency. This is the first study to address the prevalence of renal insufficiency among nursing home residents in Germany, and the extent to which such persons take drugs that are contraindicated or incorrectly dosed because of renal insufficiency.

Method: We carried out a cross-sectional study in nursing homes in the German regions of Bremen and Lower Saxony. Data were collected by nursing staff and given to us anonymously. Whenever the nursing home data did not include a current creatinine value, the patient’s general practitioner was asked to supply this value. The estimated creatinine clearance (eCCr) was calculated with the Cockcroft-Gault formula.

Results: 852 residents of 21 nursing homes were included in the study; eCCr values were obtainable for 685 (80.4%) of them (average age, 83.3 years; 75.2% female). 48.2% of these patients (95% confidence interval [CI] 41.8–54.5) had moderate renal insufficiency (eCCr 59–30 mL/min), and 15.5% (95% CI 12.4–18.6) had severe renal insufficiency (eCCr <30 mL/min). 19.7% were regularly taking at least one medication that was contraindicated or incorrectly dosed in the light of renal insufficiency. Predictors for such inappropriate drug use were advanced age, female sex, arterial hypertension, and polypharmacy. The drugs that were most often inappropriately used were metformin, ramipril, and potassium chloride.

Conclusion: Nursing home residents often suffer from renal insufficiency and should therefore have their creatinine levels measured regularly. A knowledge of the creatinine level is a prerequisite for the proper adjustment of drug doses (if necessary). A practical and compact summary of dose-adjustment recommendations for patients with renal insufficiency would be desirable but is not yet available.

About 800 000 people in Germany live in nursing homes (1). This is a population characterized by a high prevalence of chronic diseases and by physical and cognitive impairment (2–6). According to the international literature, the percentage of nursing home residents with renal insufficiency, defined as a glomerular filtration rate (GFR) of <60 mL/min, is very high, ranging between 22% and 78% (7–12). However, at present no reliable figures are available for Germany. In addition, nursing home residents often receive multiple drugs (6, 13). Since about 50% of all drugs or their metabolites are renally eliminated, this particular patient group is at considerably increased risk of inappropriate drug therapy (14). The most frequent causes of inappropriate drug therapy in older persons and nursing home residents relate to prescription (dosage too high, dose intervals too short), compliance, and/or lack of treatment monitoring (15–17). The consequences can in some cases include severe adverse drug events (AE) leading to hospital admission or even death. However, most of these AE in nursing home residents are classified as potentially avoidable or reducible (16, 17). In patients with renal insufficiency, lack of dose adjustment or the use of drugs that are contraindicated for the patient’s level of renal function are of particular significance. The few international studies that have been carried out in the nursing home setting show that 12% to 29% of residents receive at least one drug at an inappropriate dosage (18–20). The range of drugs included in the various studies varies widely. How often nursing home residents in Germany receive drugs that are not adjusted for their renal function, or are contraindicated, is unknown.

The aims of this study were therefore to investigate what percentage of nursing home residents have renal insufficiency and how often drugs are inappropriately dosed or are contraindicated for the patient’s renal function.

Methods

Data and study design

The “Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes” (IMREN) project is a multicenter cross-sectional study carried out between October 2014 and April 2015 in nursing homes in Bremen and the parts of Lower Saxony surrounding Bremen. A convenience sample was taken of nursing homes that were heterogeneous in terms of supporting organization, size, and location. Within this sample, data were recorded for all residents of the participating care units of the homes. There were no exclusion criteria.

Data collection was anonymized; data were recorded exclusively by the nursing staff in the nursing homes, using a piloted data collection form to which the patient’s current medication regimen was attached. Active participation of the residents was not required for this study, which relied exclusively on existing data. Data collected included sociodemographic information such as age and sex, height and weight, diseases present, and care level.

Up-to-date plasma creatinine concentrations were taken from care notes or hospital discharge letters; if no data were present, the care personnel requested them from the patient’s general practitioners. The glomerular filtration rate (GFR) was calculated as estimated creatinine clearance (eCCr) using the Cockcroft–Gault equation, because this is used in published studies (18–20) and as the reference in the summary of product characteristics (SPC). The Cockcroft–Gault equation includes the following variables: age, sex, body weight, and creatinine concentration (eFigure) (21).

eFigure

Equations used to estimate creatinine clearance

All data collection forms were computerized by two people independently of each other. The electronic data collection regarding medication regimens was done exclusively by pharmacists. For each drug prescribed, the summary of product characteristics was used as a basis to determine whether the drug was contraindicated or required dosage adjustment in patients with impaired renal function (eTable). Each prescription was individually assessed for whether the dosage was appropriate or the drug contraindicated for the resident’s current level of renal function. If the SPC merely mentioned dose adjustment without giving further details, we made the conservative assumption that the drugs had been correctly adjusted. All dosages were regarded as maintenance dosages. If starting dosages adjusted to the renal function had been required, this could not be taken into account because of the lack of information about treatment duration. All analyses are confined exclusively to scheduled medication. Drugs taken “as needed” and extemporaneous products were not included in the analysis.

Sample size calculation

Assuming a prevalence of renal insufficiency of 45% and an intracluster correlation coefficient of 0.01 (22), the intention was to enroll a total of 856 residents in 19 homes (n = 45 per home), in order to calculate a 95% confidence interval (95% CI) with a precision of ± 4% (41% to 49%).

Statistical analysis

All residents for whom at least one eCCr value could be computed were included. The prevalence of moderate (eCCr 59 to 30 mL/min, corresponding to stage 3 in ICD-10) and severe renal insufficiency (eCCr <30 mL/min, corresponding to stages 4 and 5) was calculated on the basis of the most recent creatinine values available. Descriptive statistics were used to analyze the baseline data. Logistic regression was used to determine which variables were associated with inappropriately dosed or contraindicated drugs for the patient’s current renal function. Predictors included in the model were age, sex, care level, polypharmacy (≥5 scheduled medications), and the most frequent co-morbidities. All analyses were cluster-adjusted; for regression analysis, mixed models with random effects were used. SAS 9.4 (SAS Institute, Cary, USA) was used for all analyses.

The study was approved by the ethics committee of the University of Bremen.

Results

Baseline data of the study population

A total of 852 residents (10 to 69 per home) of 21 homes were enrolled (11 in Bremen, 10 in the parts of Lower Saxony surrounding Bremen). At least one eCCr value could be calculated for 685 of these 852 residents (80.4%; 30% to 100% per home). The two groups (those with and those without at least one eCCr value) did not differ significantly in terms of baseline characteristics (Table 1). The analysis reported here is confined to residents with eCCr values. They had an average age of 83.3 years, three quarters of them were female, and they had been in the nursing home for an average of 3.2 years. More than a quarter of the residents had been assessed at care level III, and more than half had dementia.

Table 1

Baseline characteristics of all nursing home residents, those for whom eCCr values were available, and those for whom eCCr values were not available

Renal insufficiency

A total of 63.6% (95% CI: [55.8; 71.5]) had renal insufficiency (eCCr <60 mL/min), 48.2% of which with an eCCr of 59–30 and 15.5% with an eCCr of <30 mL/min (Table 2). A constant decline in renal function with age was shown. Thus, severe renal insufficiency (eCCr <30 mL/min) was found in 1.4% of <70-year-olds, but in 29.8% of residents aged at least 90 years. Female nursing home residents had poorer renal function than male residents, although the average age of female residents was also higher (85.0 vs. 78.3 years). The only significant difference between the sexes was in the 70 to 79 year-old age group (eCCr <60 mL/min was 12.5% [4.9; 20.1] in men and 44.0% [26.8; 61.2]) in women; however, case numbers were low.

Table 2

Prevalence of moderate and severe renal impairment (eCCr, Cockcroft–Gault equation) in nursing home residents by age and sex with a 95% confidence interval (95% CI)

The most recent creatinine value was a mean of 185 days old (interquartile range [IQR] 67 to 373). In a third of cases (31.6%) it was taken from the hospital discharge letter; in the remaining cases it was requested from the patient’s general practitioner or was recorded in the care notes. The values from both sources were of similar recency (median 185 and 188 days old, respectively). If only the 507 residents (74.1%) whose most recent creatinine values were from the previous 365 days are included, the results are the same as when all residents with recorded values are included (48.9% with an eCCr of 59 to 30 mL/min and 15.8% with an eCCr <30 mL/ min).

Medication adjustment

The 685 residents were receiving a total of 4316 drugs as scheduled medication, of which 2184 (50.6%) were potentially contraindicated or required dosage adjustment in patients with impaired renal function. The most frequently used of these were ramipril, simvastatin, and torasemide (Table 3). However, in only a small number of cases (n = 169; 7.7%) were these actually being incorrectly used in relation to the given patient’s renal function, because the drug was inappropriately dosed (n = 54) or was contraindicated (n = 115) for the patient’s eCCr value. This was most often the case for metformin, ramipril, and potassium chloride (Table 3).

Table 3

Drug prescribing

In total, 135 residents (19.7%) [15.5; 23.9] were receiving at least one drug that was inappropriately dosed or was contraindicated for their renal level of function. This was associated with higher age, female sex, arterial hypertension, and polypharmacy. Care level had no effect (Table 4).

Table 4

Prevalences and variables associated with drugs administered to nursing home residents that are inappropriately dosed or are contraindicated for the patient’s actual renal function

Discussion

Results in the context of the existing literature

This cross-sectional study showed that 63.6% of residents had renal insufficiency. To the best of our knowledge, this is the first published study of renal function in nursing home residents in Germany. Most international studies are from North America and show a very wide range of variation, with values between 22% and 78% (7–12), although some of this variation is due to known differences between the equations used to estimate creatinine clearance (23, 24). The largest study published so far enrolled 9931 residents in 87 homes in Ontario, Canada, and found an eGFR or eCCr <60 mL/min in 35.7% (“modification of diet in renal disease” [MDRD equation]) and 77.5% respectively (Cockcroft–Gault equation, which we used in our study) (11). Similar differences between the estimating equations can also be identified in our study (<60 and <30 mL/min in 63.6% and 15.5% respectively according to Cockcroft–Gault versus 41.5% and 5.5% according to MDRD). This makes clear what a large effect the choice of estimating equation has on the requirement for dose adjustment (25). Where reported, however, all studies, including our own—irrespective of which equation was used—showed renal function reducing with age, and women with lower values than men (8, 10–12).

How often nursing home residents receive drugs at inappropriate dosages or that are contraindicated for their renal function, has so far as we know only been investigated in three US studies, none of which included as large a number of different drugs as the present one (18–20). In one study of 1304 nursing home residents, in 11.9% of residents at least one of 21 drugs had not been dose-adjusted (18). In another study, 197 out of 721 residents (27.3%) received at least one of 18 drugs included in the study at an inappropriate dosage (20). The third study included all drugs that were prescribed (55 in total), but only in 90 residents. In that study, 56 residents (62%) received drugs that required dose adjustment, and in 26 (29%) at least one drug was not dose-adjusted (19). Our finding of around 20% appears comparatively low when one remembers that the larger part of our patient group (90.1%) had drugs prescribed that required adjustment or were contraindicated in patients with renal insufficiency. Regarding the frequently used drugs, there were some accordances with previous studies (e.g., allopurinol, hydrochlorothiazide, spironolactone, or gabapentin) (18, 20); other drugs, such as ranitidine, barely appeared in our study (prescribed only three times as scheduled medication). Age and polypharmacy or co-morbidities were associated with non-adjusted medication in both the larger studies (18, 20) and in our own. In the study by Hanlon et al. (18), the odds ratio for female sex was also numerically increased.

Strengths and limitations of the present study

The present study is based on a dataset of almost 700 nursing home residents prescribed about 4300 drugs as scheduled medication. Nevertheless, it is still a convenience sample of nursing homes willing to take part in a study of this kind. This means that selection bias cannot be ruled out. The same is true of the reported creatinine values, as some general practitioners, who measure serum creatinine only sporadically, may not have given information on this point. For 19.6% of residents, eCCr could not be calculated because no blood samples were taken for the purpose of the study. To do this would have required consent from the residents, which would have led to another selection bias. On the other hand, we were able to include all of the residents in the participating care units—an important point for the validity of the study. In one American study that also relied on existing data, 24% or 32% of creatinine values (depending on the calculation method used) were missing (10). The creatinine values available to us were a median of 185 days old. This does not, however, allow us to conclude with certainty that these values are measured too infrequently. A third of the values were taken from hospital discharge letters: in these cases, more recent values may exist that are unknown to the nursing homes. However, restricting the analysis to residents with values from the preceding year did not alter the prevalence of renal insufficiency.

Various equations exist for calculating the GFR, requiring different variables (e.g., cystatin C) and producing different results (8, 21, 23–26). We decided to use the Cockcroft–Gault equation, because this is commonly in routine use in clinical practice (27, 28) and in studies similar to ours (7, 11, 18–20, 23). In addition, it overestimates GFR in older persons to a much lesser extent than do the CKD-EPI and MDRD equations—an important consideration in the question of dose adjustment (28). However, restrictions in drug use in persons with impaired renal function are sometimes linked to certain other laboratory values which were not available to us and therefore could not be taken into account in this study.

To date, there is no generally accepted, uniform compilation of drugs that are contraindicated or require dose adjustment in patients with renal insufficiency (18–20, 25, 29). For this reason, we decided to rely on the SPC, since this is what is used by the personnel prescribing and supplying drugs, and is approved by regulatory authorities and regularly revised. It does, however, sometimes contain recommendations that do not reflect current evidence or routine practice; an example would be the contraindication for metformin in patients with an eGFR <60 mL/min (29–31), which after the study was concluded was lowered to <45 mL/min. Taking renal artery stenosis into consideration, and with monitoring of creatinine and potassium concentrations, even ACE inhibitors and sartans are recommended for nephroprotection (32, 33). Similarly, calcium channel blockers are used in patients with renal insufficiency to reduce blood pressure, and thiazides and related diuretics are used together with loop diuretics (33). Ultimately, it is up to the treating physician to weigh up risks against benefits, and so it can occasionally happen that even a drug that is contraindicated in patients with kidney disease is beneficial. An example is oral substitution with iron(II) sulfate, which, despite being contraindicated in patients with severe kidney disease, is, with regular monitoring, a mainstay of treatment for renal anemia (34). Other limitations of the study are discussed in the eBox.

eBox

Other limitations of the study

Conclusions

Renal insufficiency is common in residents of nursing homes. In this patient group, therefore, creatinine values should be determined at least once a year and, ideally, recorded in the care notes so as to be available to all personnel involved in the patient’s care. This would allow renal function to be taken into account even by, for example, emergency or out-of-hours physicians when prescribing. Clearly, this is not regular practice at present.

Overall, with about half of the drugs used for scheduled medication in nursing home residents, caution is needed in patients with impaired renal function. In most of the prescriptions in the present study, this had in fact been taken into account. However, in some cases it was difficult to ascertain whether and which dose adjustments were needed (e.g., for insulins, opioids, or other analgesics). Sometimes the SPC given by different manufacturers is even contradictory. This problem of divergent recommendations has also been described in the literature (25, 29). The call for a thorough review and standardization of prescribing information regarding the use of drugs in patients with renal insufficiency—as formulated in the 2008/2009 action plan for improving drug safety in Germany (35)—therefore needs repeating, with emphasis. Even in the www.dosing.de database set up by Heidelberg University Hospital, dosage recommendations are missing for some active ingredients.

Thus, there exists no unified, practical reference source for everyday clinical use where dose adjustments to be made in patients with renal insufficiency can be looked up. Given the increasing proportion of older people with multiple morbidities, this is a major problem for drug safety. A variety of approaches to a possible solution exist, which could include the following:

• Rapid harmonization of summary of product characteristics
• Integration with electronic prescribing aids or apps
• Optimization of www.dosing.de
• Producing a guideline specifically for this purpose, as was done in the Netherlands (36).

Conflict of interest statement

This study was supported financially by KfH-Stiftung Präventivmedizin. KfH-Stiftung Präventivmedizin was not involved in the data analysis and had no influence on the preparation of the manuscript or the decision to submit. The authors declare that no other conflicts of interest exist.

Acknowledgment
The authors are grateful to Mandy Köhrmann and Katharina Allers for inputting the survey form data and to Birgitt Wiese for statistical support. They thank all the participating homes for their collaboration, and Christian Scholz for technical support.

Translated from the original German by Kersti Wagstaff, MA.

Manuscript received on 21 June 2015, revised version accepted on
30 September 2015.

Corresponding author:
Prof. Dr. Falk Hoffmann, MPH
Carl von Ossietzky Universität Oldenburg
Fakultät für Medizin und Gesundheitswissenschaft
Department für Versorgungsforschung
26111 Oldenburg, Germany

@Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref0416

eBox, eFigure, eTable:
www.aerzteblatt-international.de/16m0092

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