The dangers of substance abuse in adolescents with chronic kidney disease: a review of the literature.
Abstract: Although there exist no specific data on the prevalence of substance abuse among children and adolescents with chronic kidney diseases (CKD), the magnitude of this problem should not be underestimated, as almost half of twelfth-graders in the U.S. admit to a history of using illegal drugs at least once when asked (National Institute on Drug Abuse, 2011). According to the 2010 Canadian Alcohol and Drug Use Monitoring Survey (Health Canada, n.d.), the prevalence of drug abuse among Canadian youths and young adults aged 15 to 24 remains higher than in adults older than 25 years of age, and the rates of drug use (excluding cannabis) in the past years were 7.9% and 0.8%, respectively, illustrating an almost 10 times higher rate in the younger age group (Health Canada, n.d.). Drug abuse can lead to numerous medical problems, including renal injury, and it is clearly a major public health concern, especially in patients with subnormal kidney function (Vupputuri et al., 2004). As most of the children and adolescents that suffer from CKD have long-term and trustful relationships with the nephrology team, we have the obligation and are in an excellent position to address this particular health issue (Finkelstein & Finkelstein, 2000; Kimmel, 2002; Kimmel, Cohen, & Peterson, 2008). This review summarizes the available data on the nephrotoxic effects of various commonly abused drugs with special emphasis on the additional damage that occurs in patients with pre-existing CKD. These data were obtained from a thorough search of the available primary literature, specifically using the PubMed database. The purpose is to provide health professionals with a resource to properly educate their CKD patients on the dangers of these drugs.

Key words: chronic kidney diseases, drug abuse, children
Subject: Kidney diseases (Analysis)
Kidney diseases (Risk factors)
Substance abuse (Health aspects)
Substance abuse (Analysis)
Teenagers (Health aspects)
Teenagers (Analysis)
Youth (Health aspects)
Youth (Analysis)
Authors: Steele, Melanie R.
Belostotsky, Vladimir
Lau, Keith K.
Pub Date: 01/01/2012
Publication: Name: CANNT Journal Publisher: Canadian Association of Nephrology Nurses & Technologists Audience: Trade Format: Magazine/Journal Subject: Health care industry Copyright: COPYRIGHT 2012 Canadian Association of Nephrology Nurses & Technologists ISSN: 1498-5136
Issue: Date: Jan-March, 2012 Source Volume: 22 Source Issue: 1
Product: Product Code: E121930 Youth
Geographic: Geographic Scope: Canada Geographic Code: 1CANA Canada
Accession Number: 283970443
Full Text: Objectives

After reading this article, readers should be able to:

1. Recognize that substance abuse in adolescence is common, and that adolescents suffering from chronic illness may be more predisposed to substance abuse.

2. Discuss the nephrotoxic effects of various substances of abuse in adolescents with chronic kidney disease (CKD).

3. Understand the role of the nephrology team in educating CKD patients about the risks of substance abuse.

Neurodevelopment during the adolescence period involves growth and remodelling of various areas of the brain that are associated with impulsivity and addiction, thereby predisposing them to risk-taking behaviours, including substance abuse (Chambers, Taylor, & Potenza, 2003; Crews, He, & Hodge, 2007). Health Canada has recently released the results of the 2010 CADUMS, which demonstrated that among the young individuals surveyed (aged 15 to 24), 41.4% reported lifetime use of cannabis (Health Canada, n.d.). Even more worrisome is that among these young drug users, 24.7% also reported harm to self in the past year. Children and adolescents with CKD are constantly exposed to stresses, which may further aggravate the situation. There are also studies in the literature suggesting that adolescents with chronic illnesses are more predisposed to smoking, drinking and drug addiction (Scaramuzza et al., 2010; Suris & Parera, 2005). Specifically, according to a study from the National Center on Addiction and Substance Abuse at Columbia University, nine in 10 people who suffer from drug addiction begin to smoke or drink and/or use other drugs before the age of 18 (The National Center on Addiction and Substance Abuse at Columbia University, 2011). The 2004 Canadian Addiction Survey analyzed the risks associated with tobacco use among youth aged 15 to 19, and the results indicated that tobacco use is a significant indicator for drug abuse (Davis, 2006). Studies have also suggested that young individuals are more prone to develop drug dependency and to suffer from the mental side effects, when compared to adults. Therefore, the risk of smoking and drinking behaviours among pediatric patients with chronic kidney diseases should not be underestimated (Chen, O'Brien, & Anthony, 2005; DeWit, Adlaf, Offord, & Ogborne, 2000; Raphael, Wooding, Stevens, & Connor, 2005). Moreover, it is important to keep in mind that not all adolescents will admit to drug use when asked by a health care provider. It is imperative for the team to have a high index of suspicion and be ready to provide education and guidance to adolescent patients about the risks of substance abuse. Table 1 depicts the most commonly abused drugs and their common physiologic side effects that are listed on the web page of the National Institute on Drug Abuse (n.d.). Nephrotoxicities related to drug abuse can vary according to individual situations. It may be due to the direct or indirect toxic effects of the drugs on the kidneys and may encompass a spectrum or combinations of vascular, glomerular and interstitial damage (Milroy & Parai, 2011). Table 2 depicts some common mechanisms of nephrotoxicities secondary to various drugs. The renal toxic effects of the commonly abused drugs are being discussed below. Although most of the information available in the literature originated from studies in adult patients, these experiences should also be useful in the care of adolescents.

Cannabinoids: Marijuana and hashish

Marijuana

Marijuana has different names (grass, joint, bud, Mary Jane, pot, weed and skunk) and health care providers should familiarize themselves with the names that are being used on the streets. Patients may display symptoms of euphoria, delayed reaction, poor coordination, deterioration in learning and loss of memory. According to the most recent CADUMS, the median age for the initiation of marijuana abuse among young adults was 15.7 years (Health Canada, n.d.). Despite the fact that marijuana has been one of the most commonly abused drugs in history, only a few reports of renal infarctions in patients with a history of heavy marijuana use could be found in the literature, (Lambrecht, Malbrain, Coremans, Verbist, & Verhaegen, 1995; Le Guen, Gestin, Plat, Quehe, & Bressollette, 2011). The exact mechanism has not yet been elucidated and no direct links of renal injury to its use have been established (Crowe, Howse, Bell, & Henry, 2000).

On the other hand, as cannabinoids are metabolized by the cytochrome P450 enzyme system of the liver, they may interfere with the metabolism of cyclosporine and tacrolimus, thereby increasing the risk of calcineurin inhibitor toxicities (Davison & Davison, 2011; Yamaori, Okamoto, Yamamoto, & Watanabe, 2011). As the kidney is the primary route of elimination, the risk of accumulation of the metabolites of cannabinoids increases in patients with impairment of glomerular filtration (Davison & Davison, 2011). Additionally, Bohatyrewicz et al. reported a case of a 27-year-old kidney allograft recipient who developed de novo membranous nephropathy after transplantation (Bohatyrewicz, Urasinska, Rozanski, & Ciechanowski, 2007). Even though the patient denied any previous exposure to nephrotoxic agents, his urine showed high levels of [DELTA] 9-tetrahydrocannabinol (THC) (Bohatyrewicz, et al., 2007). This case suggests a possible association between marijuana abuse and membranous nephropathy (Bohatyrewicz, et al., 2007). Moreover, a recent study from Australia provides compelling evidence that adolescents who abuse marijuana are at risk of continuing to abuse other illicit drugs later in life (Swift et al., 2011).

Opioids: Heroin and opium Heroin

Heroin is an acetylation product of morphine and has been one of the most commonly abused illicit drugs in the United States (Dettmeyer, Preuss, Wollersen, & Madea, 2005; Jaffe & Kimmel, 2006). It may be called white horse, China white or smack. It can be taken by sniffing, inhalation or injection. Although the data on heroin use among young adults are not available in the most recent CADUMS, it has also been a maorly abused drug among Canadians in the past (Fischer et al., 2005). Unlike marijuana, there is a wide spectrum of heroin-associated renal injuries, including injury secondary to rhabdomyolysis, glomerulonephropathies and interstitial nephritis (Sreepada Rao, Nicastri, & Friedman, 1977).

Renal injuries secondary to rhabdomyolysis are commonly reported among patients with heroin overdose. Various mechanisms, which include direct toxicity to muscles, pressure injuries during coma due to overdose, and allergic reactions to adulterants, have been proposed to be the etiologies of rhabdomyolysis (Cunningham, Venuto, & Zielezny, 1984; Dettmeyer, et al., 2005; Dubrow, Mittman, Ghali, & Flamenbaum, 1985; Grossman, Hamilton, Morse, Penn, & Goldberg, 1974; Kosmadakis, Michail, Filiopoulos, Papadopoulou, & Michail, 2011).

On the other hand, glomerulonephritis compatible with post-infectious acute glomerulonephritis has also been reported (Freeman, Kreps, Ronsheim, Lejano, & Sommers, 1974). The pathomechanism is probably related to the exposure to infectious agents via intravenous or subcutaneous injections (Roberts & Rabson, 1962; Tuazon, Hill, & Sheagren, 1974). Although not commonly seen in children, chronic kidney diseases associated with amyloidosis have also been documented in adult drug addicts (do Sameiro Faria, Sampaio, Faria, & Carvalho, 2003; Jaffe & Kimmel, 2006; Manner, Sagedal, Roger, & Os, 2009; Neugarten et al., 1986). Heroin-associated nephropathy (HAN) is probably the most commonly reported nephropathy among heroin addicts, particularly among African Americans addicts (Dettmeyer et al., 2005; Haskell, Glicklich, & Senitzer, 1988). Despite no uniform histological or immunofluorescence pattern being identified, patients usually present with heavy proteinuria and are at risk of rapid deterioration of renal function (Dettmeyer et al., 2005). Other renal injuries in which heroin abuse has been implicated include membranoproliferative glomerulonephritis, interstitial nephritis and granulomatous nephritis (Dettmeyer et al., 2005; Haskell et al., 1988; Sreepada Rao et al., 1977). However, it is still debatable whether these injuries are directly related to heroin or its adulterants, or the infectious contaminants such as hepatitis B and C viruses and Staphylococcus (Dettmeyer et al., 2005). Since the main metabolic byproduct of morphine, morphine-6-glucuronide, is mainly excreted through the urine, drug addicts with impaired glomerular filtration rates are predisposed to develop renal complications (Dettmeyer et al., 2005).

Stimulants: Cocaine, amphetamine and methamphetamine Cocaine

Cocaine is less commonly used among Canadian drug addicts between the ages of 15 to 24, as only 2.7% of those surveyed admitted to cocaine use in the past year (Health Canada, n.d.). Although cocaine is well known for its cardiovascular effects, cocaine abuse can also be harmful to the kidneys, and both acute and chronic kidney injuries have been associated with cocaine use in healthy individuals (Garg et al., 2011; Gitman & Singhal, 2004; Jaffe & Kimmel, 2006; Nzerue, Hewan-Lowe, & Riley, 2000). Like other commonly abused drugs, the metabolites of cocaine also rely on the kidneys as their main route of excretion and, thus, the risk of accumulation of these products is much higher in CKD patients (Churchwell & Mueller, 2007; Nzerue et al., 2000).

The most common cocaine-induced acute kidney injury is acute rhabdomyolysis (Byard, Summersides, & Thompson, 2011; van der Woude, 2000). While the exact mechanism by which cocaine causes rhabdomyolysis is unknown (Nzerue et al., 2000), it is likely due to direct myocyte toxicity, as well as ischemia resulting from vasoconstriction (Gitman & Singhal, 2004). Acute kidney injuries have also been reported in cocaine users who developed anti-glomerular basement membrane glomerulonephritis and interstitial nephritis (Nzerue et al., 2000; Sirvent et al., 2007; Wojciechowski, Kallakury, & Nouri, 2008). The exact mechanism is still unknown, but it may be related to the endothelial damage induced by cocaine that leads to antibody production (Nzerue et al., 2000). Cocaine can also lead to renal vascular diseases and malignant hypertension, thus induce acute kidney injury by vasoconstriction (Gitman & Singhal, 2004; Gu & Herrera, 2007; Nzerue et al., 2000). It may also lead to thrombotic microangiopathy and endothelial damage by not-yet-understood mechanisms (Gitman & Singhal, 2004; Gu & Herrera, 2007; Jaffe & Kimmel, 2006).

It is speculative that cocaine abuse is more likely to induce injury in patients with underlying renal insufficiencies by hastening the progression of renal disease. A recent study has also shown that cocaine users developed end stage renal diseases and required dialysis at younger ages than the group not using cocaine (Gitman & Singhal, 2004).

Amphetamines

Amphetamines have been implicated in different forms of renal diseases (Citron et al., 1970; Halpern & Citron, 1971; Koff, Widrich, & Robbins, 1973; White, 2002). Acute kidney injuries secondary to rhabdomyolysis have been associated with intravenous use of methamphetamines (Ginsberg, Hertzman, & Schmidt-Nowara, 1970; Kendrick, Hull, & Knochel, 1977). Furthermore, necrotizing angiitis has also been described in adult amphetamine abusers (Citron et al., 1970). Initial presentations include constitutional symptoms such as weight loss, fever and chronic fatigue, and then progress to severe abdominal and joint pain, cutaneous rashes and ulcers (Citron et al., 1970). Patients with renal involvement usually have hematuria, proteinuria, rapid progression of hypertension and worsening of renal function, with histological findings that are very similar to polyarteritis nodosa (Halpern & Citron, 1971). Interstitial nephritis has also been reported, and some of these patients recovered with corticosteroid therapy (Foley, Kapatkin, Verani, & Weinman, 1984).

Methylenedioxymethamphetamine, also known as ecstasy, is another amphetamine that has been very popularly abused at rave parties (Crowe et al., 2000). Besides acute renal injuries due to rhabdomyolysis, there are other case reports on ecstasy abusers who suffered from hyponatremia, necrotising vasculitis, proximal tubulopathy and chronic kidney diseases (Bingham, Beaman, Nicholls, & Anthony, 1998; Campbell & Rosner, 2008; Kwon, Zaritsky, & Dharnidharka, 2003; Woodrow & Turney, 1999).

Dissociative drugs: Phencyclidine and ketamine

Phencyclidines

Phencyclidine (PCP) is commonly known as angel dust, crystal and hog (Cogen, Rigg, Simmons, & Domino, 1978). Consumption of low doses is typically associated with euphoria, but ingestion in large dose can cause severe complications, such as hypertension, hyperthermia and rhabdomyolysis (Akmal, Valdin, McCarron, & Massry, 1981; Bey & Patel, 2007).

Ketamine

Ketamine is a commonly used anesthetic drug with amnesic effect. It is structurally related to PCP and is also known as special K. Case reports have linked ketamine use to the development of inflammatory cystitis and acute renal injury (Chu et al., 2007; Selby et al., 2008; Shahani, Streutker, Dickson, & Stewart, 2007).

Hallucinogens: Lysergic acid diethylamide and psilocybin mushroom

Although hallucinogens such as lysergic acid diethylamide and psilocybin mushroom have potent psychotic effects, adverse renal effects are also possible. Renal injuries due to rhabdomyolysis have been reported in individuals using Lysergic acid diethylamide (Berrens, Lammers, & White, 2010; Mercieca & Brown, 1984). Additionally, acute renal injuries that required renal replacement therapies have also been reported in individuals after consumption of the Psilocybe specis mushroom (Bickel et al., 2005; Raff, Halloran, & Kjellstrand, 1992). The exact mechanism of renal injury is still unclear, but renal biopsies from these victims showed medullary edema and necrosis of tubular cells (Bouget et al., 1990; Holmdahl, Mulec, & Ahlmen, 1984).

Others: Commonly abused drugs

Prescription drugs with addictive effects

Prescription drug abuse, including hydrocodone and benzodiazepines, is one of the fastest growing addiction problems. According to the 2011 estimated world requirements of narcotic drugs, Canadians rank third for top consumers of oxycodone, only after France and the United States, and are the top users of hydromorphone (Estimated World Requirements of Narcotic Drugs for 2011, October update). Although there are no nephrotoxic effects reported in patients who abuse hydrocodone, there is evidence that benzodiazepine overdose may lead to renal injuries including rhabdomyolysis and interstitial nephritis in patients with pre-existing chronic renal diseases (Hojgaard, Andersen, & Moller-Petersen, 1988; Sadjadi, McLaughlin, & Shah, 1987).

Inhalants

The inhalation of different types of volatile solvents has been reported in the literature (Meadows & Verghese, 1996). Among the commonly abused solvents, such as glue, thinner, gasoline, correction liquids and toluene, only toluene has been reported to cause renal injuries (Flanagan, Meredith, & Ramsey, 1989; Gupta, van der Meulen, & Johny, 1991; Kamijima et al., 1994; Patel & Benjamin, 1986; Ramsey, Anderson, Bloor, & Flanagan, 1989). The presentation of renal injuries is protean, ranging from mild symptoms such as microscopic hematuria, proteinuria, and pyuria, to more severe damage with long-term consequences, such as tubular injury, glomerulonephritis, interstitial nephritis, nephrolithiasis and Goodpasture's syndrome (Bonzel et al., 1987; Gupta et al., 1991; Kaneko, Koizumi, Takezaki, & Sato, 1992; Kondo et al., 1995; Russ, Clarkson, Woodroffe, Seymour, & Cheng, 1981; Streicher, Gabow, Moss, Kono, & Kaehny, 1981; Taverner, Harrison, & Bell, 1988; Venkataraman, 1981). However, the exact mechanisms of such injuries are still unclear (Kaneko et al., 1992).

Ethanol

Although alcohol is not an illegal drug in Canada, it is a commonly consumed beverage in adolescents that has the potential for harmful effects. Alcohol was used during the past 30 days in 52.3% of youth surveyed in the 2010 CADUMS report (Health Canada, n.d.). Binge drinking in the past month has also been reported in 22.3% of students in grades 7 to 12 according to the Ontario Student Drug Use and Health Survey (OSDUHS) (Paglia-Boak, 2011). Long-term consumption of ethanol can have many deleterious effects on kidney function. Chronic alcoholism has been shown to cause acute tubular necrosis and dysfunction (De Marchi et al., 1993; Presti, Carollo, & Caimi, 2007). An autopsy series on chronic alcoholics demonstrated a high incidence of IgA deposition in the kidneys, which suggested the possible association of chronic alcoholism and IgA nephropathy (Cecchin & De Marchi, 1996). Furthermore, there are cases of acute kidney injuries resulting from alcohol-induced rhabdomyolysis (Haapanen, Pellinen, & Partanen, 1984). Lastly, ethanol consumption has also been implicated in hypertension when consumed in amounts greater than 80 g daily in men and greater than 40 g daily in women (Vamvakas, Teschner, Bahner, & Heidland, 1998). Electrolyte abnormalities such as salt and water retention, and renal loss of calcium, phosphate and magnesium due to alcohol-induced hypoparathyroidism have also been linked to chronic alcoholism (Vamvakas, et al., 1998). Moreover, long-term alcohol consumption is also associated with hyperuricemia and predisposition to gout (Vamvakas, et al., 1998). Thus, alcohol consumption should be discouraged in patients with pre-existing CKD, as they would be at higher risk for these alcohol-related kidney injuries.

Ethylene glycol

The ingestion of antifreeze, or other forms of ethylene glycol (EG), often results in acute renal failure. U.S. poison centre statistics show that about 5,000 people are treated for EG poisoning in the United States every year, with about 20 to 40 fatalities (Bronstein et al., 2009). The mechanism has not been established, but is thought to result from the production of a toxic metabolite. Although the "aldehyde" metabolites of EG, glycolaldehyde, and glyoxalate have been suggested as the metabolites responsible, recent studies have shown definitively that the accumulation of calcium oxalate monohydrate (COM) crystals in kidney tissue produce renal tubular necrosis that leads to kidney failure (McMartin, 2009). The blockade of EG metabolism with fomepizole (or ethanol) to prevent formation of glycolate and oxalate is the mainstay of current therapy for early stages of EG poisoning. However, there are significant numbers of patients who remain undiagnosed, either because of delay in getting to a hospital or difficulties in making the diagnosis (Jacobsen, 1999). In these cases, EG metabolism will have occurred before diagnosis, thus leading to serious morbidity, including COM-induced renal failure. The only current treatment for EG-induced renal failure is hemodialysis/ hemodialfiltration.

Tobacco

Tobacco use is widespread, making it the greatest cause of morbidity and mortality in the United States (Ehlers et al., 2006). While tobacco is notorious for its damaging effects on the respiratory and cardiovascular systems, there is also evidence for its harmful effects on the kidneys. Firstly, tobacco use increases the risk for kidney cancers such as renal cell carcinoma (Cooper, 2006). Furthermore, nicotine, a component of tobacco, has been shown to worsen proteinuria (Cooper, 2006). Smoking has been shown to increase the risk of developing microalbuminuria in healthy individuals (Hillege et al., 2001) and accelerate the progression of CKD in diabetic patients (Cooper, 2006). A prospective study in hypertensive patients has also suggested that smoking is one of the major risk factors of renal function deterioration (Regalado, Yang, & Wesson, 2000). Among renal allograft recipients, smoking has also been associated with higher rates of graft loss (Kasiske & Klinger, 2000; Sung, Althoen, Howell, Ojo, & Merion, 2001).

The role of nephrology nurses

As nephrology nurses have had long-term and trustful relationships with the adolescents with CKD, they are, thus, in the best position to help those who are struggling with substance abuse at different levels. Hence, it is pivotal for nephrology nurses to keep abreast of their knowledge regarding how to detect the signs and symptoms of drug abuse and familiarize themselves with the relevant resources within their community. As it is not the routine for the nephrology team to screen their patients, it is imperative that we have a high index of suspicion, especially in those at high risk for drug abuse, including those with a co-existing psychiatric illness and a family history of substance abuse (Leslie, 2008; Swadi, 1999). Signs may be subtle and easily missed, such as non-adherence to a therapeutic regimen and mood instability. If in doubt, the physicians need to be notified for further evaluations. There are a number of validated clinical tools that can be used in adolescents for assessment of substance abuse, including the Personal Experience Screening Questionnaire (PESQ), Alcohol Use Disorders Identification Test (AUDIT) and the CRAFFT Screening Test (Knight, Sherritt, Shrier, Harris, & Chang, 2002; Saunders, Aasland, Babor, de la Fuente, & Grant, 1993; Winters, 1992). The authors find their colleagues in the Adolescence Medicine and Clinical Psychology Departments particularly helpful in administering these tests. When intervention is necessary, the nephrology team can work with the family to arrange counselling and psychological support. It is not the intention of the authors to discuss the community resources for youth suffering from drug abuse; rather, it is recommended that readers refer to the National Anti-Drug Strategy website of the Government of Canada for further information.

Conclusion

Adolescents are at a neurodevelopmental stage that renders them more prone to addiction, and there is substantial evidence that such behaviour has significant health consequences. The deleterious effects of drug abuse on the kidney, especially in patients with pre-existing renal insufficiencies, cannot be over emphasized. Since experimenting with various drugs is common in the teenage years, it is crucial for pediatric patients with CKD to recognize that they are particularly vulnerable to the complications. It is the responsibility of the renal team to be their advocates and provide advice and guidance. Nephrology nurses are in a position to recognize and assist adolescents who suffer from CKD and substance abuse by screening for related signs and referring them to appropriate counselling services.

RELATED ARTICLE: The dangers of substance abuse in adolescents with chronic kidney disease: a review of the literature

By Melanie R. Steele, Vladimir Belostotsky, MD, PhD, MRCPCH, and Keith K. Lau, MBBS, FAAP, FRCPCH

1. A 14-year-old renal transplant recipient admits to smoking marijuana on the weekends with his friends. This is concerning because of the risk of:

(a) drug interactions

(b) rhabdomyolysis

(c) interstitial nephritis

(d) granulomatous nephritis

2. Alcohol consumption in a patient with CKD can be associated with all of the following, except:

(a) rhabdomyolysis

(b) acute tubular necrosis

(c) membrano-proliferative nephropathy

(d) electrolyte abnormalities

3. What is the most common nephropathy among heroin users?

(a) post-infectious acute glomerulonephritis

(b) heroin-associated nephropathy

(c) rhabdomyolysis

(d) membranoproliferative glomerulonephritis

4. Which of these statements is NOT true about cocaine?

(a) cocaine users require dialysis at younger ages than non-cocaine users

(b) cocaine is solely metabolized by the liver

(c) cocaine use can lead to acute rhabdomyolysis

(d) cocaine use can lead to renal vascular disease

5. Nephrotoxic effects have been reported in patients that abuse all of the following, except:

(a) benzodiazepines

(b) ecstasy

(c) amphetamines

(d) hydrocodone

6. Which of the following substances has been reported to be associated with higher rates of graft loss in renal allograft recipients?

(a) marijuana

(b) red wine

(c) cigarettes

(d) ketamine

7. Which commonly abused solvent is known to cause renal injuries?

(a) glue

(b) toluene

(c) gasoline

(d) thinner

8. A reasonable way to approach an adolescent with CKD and suspected substance abuse is to:

(a) use the Personal Experience Screening Questionnaire (PESQ)

(b) notify the patient's parents

(c) notify the police

(d) order a urine toxicology screen

9. Which of the following is true about adolescents?

(a) 41.4% of Canadian adolescents reported lifetime use of cocaine

(b) adolescents with chronic illnesses are less likely to smoke compared with healthy adolescents

(c) adolescents are less likely to develop drug dependency compared to adults

(d) not all adolescents will admit to drug use when asked by a health care provider

10. Which of the following characteristics would cause the nephrology team to screen an adolescent for substance abuse?

(a) family history of substance abuse

(b) male

(c) diabetic

(d) family history of CKD

RELATED ARTICLE: The dangers of substance abuse in adolescents with chronic kidney disease: a review of the literature

By Melanie R. Steele, Vladimir Belostotsky, MD, PhD, MRCPCH, and Keith K. Lau, MBBS, FAAP, FRCPCH

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Melanie R. Steele, Medical Student, Faculty of Health Sciences, McMaster University, Hamilton, ON.

Vladimir Belostotsky, MD, PhD, MRCPCH, Assistant Professor, Department of Pediatrics, McMaster University, Hamilton, ON.

Keith K. Lau, MBBS, FAAP, FRCPCH, Associate Professor, Department of Pediatrics, McMaster University, Hamilton, ON.

Address correspondence to: Keith K. Lau, MBBS, FAAP, FRCPCH, Department of Pediatrics, McMaster University, 1280 Main Street West, HSC 3A, Hamilton, ON L8S 4K1.

Tel: (905) 521 2100 ext. 75635; Fax: (905) 308 7548; Email: kelau@mcmaster.ca

Submitted for publication: October 25, 2011.

Accepted for publication in revised from: January 31, 2012.

By Melanie R. Steele, Vladimir Belostotsky, MD, PhD, MRCPCH, and Keith K. Lau, MBBS, FAAP, FRCPCH
Table 1. Commonly abused drugs and their physiologic effects

Adapted from the web page of the National Institute on Drug Abuse
(National Institute on Drug Abuse).

Drugs                          Physiologic Effects

Cannabinoids   Euphoria; decreased coordination; memory and
               learning impairment; delayed reactions; increased
               heart rate; increased appetite; anxiety

Opioids        Euphoria; sedation; nausea; confusion;
               constipation; respiratory depression; infectious
               disease

Stimulants     Energetic; increased irritability; sleeping
               difficulties; increased body temperature, blood
               pressure and heart rate; loss of appetite and
               weight loss; violence; anxiety; paranoia; tremors;
               cardiovascular complications; seizures; stroke

Dissociative   Feelings of separation from oneself; memory
drugs          impairment; nausea; tremors; analgesia;
               hallucinations; violent behaviours; coordination
               difficulties; psychosis

Hallucinogens  Increased blood pressure, heart rate and body
               temperature; distorted perception; Hallucinogen
               Persisting Perception Disorder; insomnia;
               impulsivity; emotional instability; reduced
               appetite; tremor; dizziness; flashbacks

Inhalants      Varies depending on the specific chemical. Possible
               effects include: weakness; impaired coordination;
               headache; lowered inhibitions; impaired memory;
               decreased level of consciousness; nausea and
               vomiting; depression; cardiovascular effects;
               neurologic effects

Ethanol        Euphoria; lowered inhibitions; lethargy; nausea;
               emotional instability; decreased level of
               consciousness; memory impairment; violent
               behaviours; liver damage; cardiovascular disease;
               hypertension

Tobacco        Respiratory and cardiovascular disease; CVA;
(nicotine)     increased heart rate and blood pressure; various
               cancers

Table 2. Nephrotoxicities associated with various drugs of abuse

Drugs                        Associated nephrotoxicities reported in
                                            literature

Cannabinoids                Drug interactions (via cytochrome P450)
Opioids                     Rhabdomyolysis Glomerulonephropathies
                            (including heroin associated
                            nephropathy) Membranoproliferative
                            glomerulonephritis Interstitial nephritis
                            Granulomatous nephritis

Cocaine                     Rhabdomyolysis Anti-glomerular basement
                            membrane glomerulonephritis Interstitial
                            nephritis Renal vascular diseases
                            Infarction Malignant hypertension
                            Thrombotic microangiopathy

Amphetamines                Rhabdomyolysis Necrotizing angiitis
                            Interstitial nephritis

MDMA
(ecstasy)                   Rhabdomyolysis Necrotising vasculitis
                            Proximal tubulopathy

Phencyclidines              Rhabdomyolysis Hypertension

Ketamine                    Inflammatory cystitis

Lysergic Acid Diethylamide  Rhabdomyolysis Medullary edema Tubular
and Psilocybin              cell necrosis

Benzodiazepines             Rhabdomyolysis Interstitial nephritis

Inhalants                   Microscopic hematuria, proteinuria,
                            pyuria Tubular injury Glomerulonephritis
                            Interstitial nephritis Nephrolithiasis
                            Goodpasture's syndrome

Ethanol                     Acute tubular necrosis IgA nephropathy
                            Rhabdomyolysis Hypertension Electrolyte
                            abnormalities Hyperuricemia

Ethylene glycol             Acute renal failure Renal tubular
                            necrosis COM-induced renal failure

Tobacco                     Renal cell carcinoma Proteinuria Kidney
                            allograft loss in transplant recipients


Post-test answer grid

Please circle your answer choice:

1.   a  b  c  d
2.   a  b  c  d
3.   a  b  c  d
4.   a  b  c  d
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7.   a  b  c  d
8.   a  b  c  d
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10.  a  b  c  d
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