Concealed renal insufficiency and adverse drug reactions in elderly hospitalized patients.

BACKGROUND Adverse drug reactions (ADRs) are common causes of in-hospital complications for elderly people. The purpose of the present study is to verify whether concealed renal insufficiency, that is, reduction of the estimated glomerular filtration rate (GFR) in people with normal serum creatinine levels, is a risk factor for ADRs in elderly hospitalized patients. METHODS We used data on 11,687 hospitalized patients enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. The outcomes of the study were any ADR, ADR to hydrosoluble drugs, and ADR to any other drug during the hospital stay. We compared 3 groups: normal renal function (normal serum creatinine levels and normal estimated GFRs), concealed (normal serum creatinine levels and reduced estimated GFRs), or overt (increased creatinine levels and reduced estimated GFRs) renal insufficiency. The relationship between renal function and ADR was evaluated using contingency tables and multiple regression analysis including potential confounders. RESULTS Concealed renal insufficiency was detected in 1631 (13.9%) patients and was frequently associated with male sex and poor nutritional status. Hydrosoluble drugs were responsible for 301 of the 941 recorded ADRs. After adjusting for potential confounders, both concealed (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.15-1.25) and overt (OR, 2.02; 95% CI, 1.54-2.65) renal failure were associated with ADR to hydrosoluble drugs, but not with ADR to other drugs (OR, 0.83 [95% CI, 0.65-1.08], and OR, 1.01 [95%CI, 0.83-1.23], respectively). CONCLUSION Older hospitalized patients frequently have impaired renal function despite normal serum creatinine levels and are exposed to an increased risk of ADRs to hydrosoluble drugs.

[1]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[2]  W. Rocca,et al.  Validation of the Hodkinson abbreviated mental test as a screening instrument for dementia in an Italian population. , 1992, Neuroepidemiology.

[3]  S. Fukumoto,et al.  Factors affecting progression of renal failure in patients with type 2 diabetes. , 2003, Diabetes care.

[4]  Kdoqi Disclaimer K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[5]  F. Follath,et al.  Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine. , 2000, British journal of clinical pharmacology.

[6]  M. Pahor,et al.  Pharmacosurveillance in hospitalized patients in Italy. Study design of the 'Gruppo Italiano di Farmacovigilanza nell'Anziano' (GIFA). , 1999, Pharmacological research.

[7]  Roberto Bernabei,et al.  Is Age an Independent Risk Factor of Adverse Drug Reactions in Hospitalized Medical Patients?* , 1991, Journal of the American Geriatrics Society.

[8]  J L Bootman,et al.  Drug-related morbidity and mortality. A cost-of-illness model. , 1995, Archives of internal medicine.

[9]  D. Classen,et al.  Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. , 1997, JAMA.

[10]  S. Mcphee,et al.  Current Medical Diagnosis and Treatment , 2009, Journal of Nuclear Medicine.

[11]  K. J. Lutz,et al.  A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women. , 1991, Journal of applied physiology.

[12]  J. Erikssen,et al.  Drug-related deaths in a department of internal medicine. , 2001, Archives of internal medicine.

[13]  David W. Hosmer,et al.  Applied Logistic Regression , 1991 .

[14]  W. Stigelman,et al.  Goodman and Gilman's the Pharmacological Basis of Therapeutics , 1986 .

[15]  R. Bressler,et al.  Principles of drug therapy for the elderly patient. , 2003, Mayo Clinic proceedings.

[16]  J. Lea,et al.  Diabetes mellitus and hypertension: key risk factors for kidney disease. , 2002, Journal of the National Medical Association.

[17]  B. Astor,et al.  Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease. , 2004, Kidney international.

[18]  O Pelkonen,et al.  Age and cytochrome P450‐linked drug metabolism in humans: An analysis of 226 subjects with equal histopathologic conditions , 1997, Clinical pharmacology and therapeutics.

[19]  R. Lindeman,et al.  Assessment of renal function in the old. Special considerations. , 1993, Clinics in laboratory medicine.

[20]  D. Greenblatt,et al.  A method for estimating the probability of adverse drug reactions , 1981, Clinical pharmacology and therapeutics.

[21]  M. Sager,et al.  Adverse drug events in hospitalized elderly. , 1998, The journals of gerontology. Series A, Biological sciences and medical sciences.

[22]  Quan Dong Nguyen,et al.  Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. , 2003, JAMA.

[23]  H. Beijer,et al.  Hospitalisations caused by adverse drug reactions (ADR): a meta-analysis of observational studies , 2002, Pharmacy World and Science.

[24]  J. M. Guralnik,et al.  Drug data coding and analysis in epidemiologic studies , 1994, European Journal of Epidemiology.

[25]  M. Cesari,et al.  Adverse Drug Reactions as Cause of Hospital Admissions: Results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA) , 2002, Journal of the American Geriatrics Society.

[26]  K. Turnheim When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly , 2003, Experimental Gerontology.

[27]  W. Ambrosius,et al.  The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity , 2003, Clinical pharmacology and therapeutics.

[28]  Kay Brune,et al.  Identification of Adverse Drug Reactions in Geriatric Inpatients Using a Computerised Drug Database , 2003, Drugs & aging.

[29]  Ethan M Balk,et al.  K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[30]  S. Knowles,et al.  Gender Differences in Adverse Drug Reactions , 1998, Journal of clinical pharmacology.

[31]  J. Schwartz The Influence of Sex on Pharmacokinetics , 2003, Clinical pharmacokinetics.

[32]  P. Corey,et al.  Incidence of Adverse Drug Reactions in Hospitalized Patients , 2012 .