SUBSTANCE ABUSE AND YOUR KIDNEYS - The Kidney Protector

Table of Contents

SUBSTANCE ABUSE AND YOUR KIDNEYS: THE KIDNEY DIALOGUES: SPECIAL EDITION!

YOUR KIDNEYS AND ILLICIT DRUG USE aka SUBSTANCE ABUSE or DRUG ABUSE

SUBSTANCE ABUSE, YOUR LIFE AND YOUR KIDNEYS!

Substance Abuse and your kidneys is a topic that deserves your attention. Illicit drugs vary in type, effects, risks and potential morbidity and mortality meaning the possibility of sickness and death. Substance abuse transcends economic status and is dangerous with the potential to ruin talent, lives, devastate families and negatively impact whole populations. However, many people are not aware that drugs/substances of abuse can damage kidneys. Substances of abuse can damage the kidneys suddenly, called Acute kidney injury [AKI] or over longer periods of time, called Chronic Kidney Disease [CKD].

10+ Things That Can Harm Kidneys include Illicit Drugs/Substance Abuse

How Does Substance Abuse Harm Kidneys?

Substance abuse can harm kidneys by:

Harmful effect of the drug itself (see below)
Harmful effects due to the method of use: for example IV drug use results in numerous harmful effects (9) including inflammation (interstitial inflammation), interstitial fibrosis, in addition to deposition of calcium in the kidneys (renal parenchymal calcification)
Harmful effects of adulterants (otherwise know as fillers or cutters)

The most commonly known substances of abuse are (and by the way they can ALL damage your kidneys):

Cocaine
Heroin and other opioids
Cannabis and Synthetic Cannabinoids
Methamphetamines
Bath salts
Cigarettes/Tobacco (yup!)
Anabolic steroids
Alcohol

Cocaine: damages the kidneys by rhabdomyolysis: which means killing muscle cells: the biproducts of dead muscle cells can seriously damage kidneys, sometimes visible as brown urine as the muscle component myoglobin spills in the urine. Cocaine also damages kidneys by increasing the blood pressure to dangerously high levels or by the effects of fillers/cutters (see below)
Heroin and other opioids: damages kidneys by heroin associated nephropathy. Repeated occurrence of inflammation and infections results in a condition called AA Amyloidosis, FSGS. Heroin can also damage the kidneys via rhabdomyolysis, heroin crystal nephropathy and in Black patients with APOL1 risk alleles who have HIV or Hepatitis C, additional risk of APOL1 nephropathy may exist

Cannabis and Synthetic Cannabinoids: marijuana can damage the kidneys if dehydration results from vomiting due to excessive use. Synthetic cannabinoids have been observed to cause acute kidney injury (AKI) and wont show on toxicology screens so you MUST tell your doctor if you have used those so you can get the best care! If you have type 1 Diabetes, special caution: these drugs increase your risk of DKA (diabetic ketoacidosis) so please avoid using.

Methamphetamine: Methylenedioxymethamphetamine (MDMA) aka Ecstasy: harmful to kidneys! How? They can cause rhabdomyolysis and therefore acute kidney injury (AKI). Ecstasy can also cause a dangerous lowering of sodium that needs emergency medical attention: a condition called Hyponatremia. Methamphetamines can also cause high blood pressure, abnormal heart rhythms, difficulty breathing and brain swelling (fancy terms: hypertension, arrhythmia, pulmonary edema and cerebral edema). Bonus: they can also cause liver failure ☹

Bath Salts (Synthetic Cathinone): Can harm your kidneys by causing rhabdomyolysis and can also cause a very high uric acid level called hyperuricemia which can damage your kidneys and more!

Cigarettes (unexpected but true): harm your kidneys by increasing the risk of Chronic Kidney Disease (CKD) and End Stage Kidney Disease (ESKD aka ESRD). It increases the risk of protein in your urine. Even Passive smoking increases your risk of kidney disease so avoid hanging out with smokers, avoid being around smokers!

Anabolic Steroids: harms kidneys by causing protein to spill in the urine! IF you quit these drugs there is a good chance of recovery of the damage to the kidneys. Causes a kidney condition called FSGS.
Alcohol: harms kidneys by elevating the blood pressure. Can also cause harm to kidneys through dehydration (called volume depletion by kidney specialists)

ADULTERANTS (aka Fillers/Cutters)

The issue of adulterants otherwise known as drug fillers or cutting agents, deserves special attention (4,10). The affected drugs are typically cocaine, heroin, and fentanyl (4). Separate from the fillers/cutters, substances may be adulterated with other substances like cocaine being adulterated with fentanyl: that form of adulteration is very important is outside of the scope of this topic but is a very important public health crisis (11) as it pertains to drug overdose deaths.

Cocaine is an important example: It can harm the kidneys via Acute Kidney Injury (AKI) by rhabdomyolysis (death of muscle cells), via the effects of hypertensive emergencies (malignant hypertension), thrombotic microangiopathy (TMA), or, if adulterated with levamisole: an ANCA vasculitis.

Adulterants include:

Caffeine (good ole caffeine!)
Levamisole (an antihelminthic medication for animals: used to treat worm infections in horses etc! Side effects include severe kidney injury, vasculitis and neutropenia/agranulocytosis: a low white blood cell count which predisposes to severe infections. Levamisole is an active isomer of racemic tetramisole.
Phenacetin (previously discontinued analgesic/painkiller: discontinued due to cancer risk and kidney failure risk, see details below)
Lidocaine (numbing agent also used to treat arrhythmias)
Tetramisole: an antihelminthic agent used to treat worm infections: Ascaris lumbricoides

These “Fillers” are harmful like the vasculitis-inducing levamisole found in cocaine known to cause severe acute kidney injury in addition to the other ways cocaine by itself can induce kidney injury. Separate from the above fillers, substances may be adulterated with other substances like cocaine being adulterated with fentanyl: that form of adulteration is outside of the scope of this topic.

There is now a rise in the incidence of adulteration of illicit drugs with phenacetin (possibly for its sedative effects). Unfortunately, street drugs are commonly adulterated with phenacetin as the filler at rates of 3% to 60% depending on the State of location in the US. For example, prior data shows 42.5% of samples tested in Florida were adulterated by phenacetin. Most people suffering from substance abuse disorders are not aware. The substances that have been found to be contaminated with phenacetin are Cocaine, heroin, and fentanyl. However, cocaine is the most common of the three.

The issue of phenacetin adulteration adds significantly to the morbidity and mortality associated with substance abuse and empowering people with this knowledge can help save lives and kidneys.

Phenacetin

Phenacetin adulteration street drugs is a profound one of deserves alarm as the issue is now widespread. In the past, phenacetin (an analgesic or painkiller) was discontinued (removed from the market) due to significant adverse effects of kidney failure due to a condition called analgesic nephropathy, in addition to increased risk of cancer of the kidney, renal pelvis, ureter, and bladder. It was discontinued and withdrawn from the market in 1983 in the United States of America, 1980 in the United Kingdom, in 1978 in Canada, and banned in Australia in 1977. It is still legal in Hungary as a medication called Antineurlgica and Dolor as reported by the publication “Phenacetin” by the International Agency for Research on Cancer (IARC).

Getting Help

If you are suffering from substance abuse and would like more information about help, please visit the Substance Abuse and Mental Health Administration (SAMHSA.gov). For additional information, including how substance abuse affects your kidneys and how to get help, visit this helpful site and the national kidney foundation. If you are a social worker or other supporting team member in kidney care, see this helpful article from the national kidney foundation!

References

1. Amanda L.A. Mohr, MS; Thom Browne, MA; Lewis Nelson MD, and Barry K. Logan, PhD. Public Health Alert. Phenacetin: A Toxic Adulterant Found in Illicit Street Drugs “This report was prepared by Amanda L.A. Mohr, MS; Thom Browne, MA; Lewis Nelson MD, and Barry K. Logan, PhD.
Funding for this document was received by the Fredric Rieders Family Foundation from the Colombo Plan via U.S. Department of State/INL under
2019-RG-061 and 2017-RG-61, and other Colombo Plan funding sources. “

2. Fiorentin TR, Krotulski AJ, Martin DM, Browne T, Triplett J, Conti T, Logan BK. Detection of Cutting Agents in Drug-Positive Seized Exhibits within the United States. J Forensic Sci. 2019 May;64(3):888-896. doi: 10.1111/1556-4029.13968. Epub 2018 Nov 28. PMID: 30485426.

3. Nadia Fucci. Phenacetin and cocaine in a body packer. Forensic Science International. Volume 141, Issue 1, 2004: Pages 59-61. ISSN 0379-0738,
https://doi.org/10.1016/j.forsciint.2003.12.012.(https://www.sciencedirect.com/science/article/pii/S0379073804000039)
Abstract: A case of acute intoxication of cocaine adulterated with phenacetin is reported. Twenty-four packages were found in the stomach and intestine of a 25-year-old male. The identification of phenacetin was performed by gas chromatography-mass spectrometry (GC/MS) analysis.

4. Rui Gameiro, Suzel Costa, Mário Barroso, João Franco, Suzana Fonseca. Toxicological analysis of cocaine adulterants in blood samples. Forensic Science International: Volume 299, 2019, Pages 95-102. ISSN 0379-0738, https://doi.org/10.1016/j.forsciint.2019.03.005.
Abstract: Cocaine was the second most widely used drug in Europe in 2016, with 3.5 million consumers aged 15–64 years old. Adulterants are pharmacologically active substances developed for medical purposes, however, there is little knowledge about their influence in the human body when there is concomitant use with cocaine. The objective of this work was to validate a method that allows the identification, confirmation and quantification of cocaine adulterants in blood samples collected in vivo or post-mortem. The studied substances were atropine, phenacetin, hydroxyzine, ketamine, lidocaine and tetramisole. A retrospective study of the prevalence of these substances, as well as their relative concentrations, was made analysing 97 real blood samples previously tested positive for cocaine and/or its metabolites. The analytes of interest were extracted, using a simple method based on protein precipitation with frozen acetonitrile and further analysis by GC/MS. The method was fully validated in accordance with parameters and criteria implemented in the lab and SWGTOX recommendations (mean recovery: 94–115%; CV: 6.2–13%; BIAS: 2.7–7.8%). 31 samples were positive for adulterants: phenacetin (19%), tetramisole (15%), lidocaine (8%) and hydroxyzine (1%). Concentrations were higher in post-mortem samples for all compounds analysed. Lidocaine was more prevalent in samples collected in vivo whereas tetramisole was present almost exclusively in post-mortem samples. Phenacetin was evenly distributed between post-mortem and in vivo samples. The validated method allows rapid, precise, accurate and economic analysis of selected compounds and requires smaller sample aliquots which can be important in post-mortem cases. The information collected can be important in future studies of correlation between the presence of adulterants and cocaine toxicity.

5. Phenacetin. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Pharmaceuticals. Lyon (FR): International Agency for Research on Cancer; 2012. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 100A.)

6. Satyavan Sharma, Nitya Anand; Approaches to Design and Synthesis of Antiparasitic Drugs in Pharmacochemistry Library, 1997;

7. Stephen W Page, David B Church; Antiparasitic drugs in Small Animal Clinical Pharmacology (Second Edition), 2008: Pages 198-260, ISBN 9780702028588

8. Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. Mayo Clin Proc. 2012 Jun;87(6):581-6. doi: 10.1016/j.mayocp.2012.03.010. PMID: 22677078; PMCID: PMC3498128.

9. Buettner M, Toennes SW, Buettner S, Bickel M, Allwinn R, Geiger H, Bratzke H, Amann K, Jung O. Nephropathy in illicit drug abusers: a postmortem analysis. Am J Kidney Dis. 2014 Jun;63(6):945-53. doi: 10.1053/j.ajkd.2014.01.428. PMID: 24823296.

10. Cole C, Jones L, McVeigh J, Kicman A, Syed Q, Bellis M. Adulterants in illicit drugs: a review of empirical evidence. Drug Test Anal. 2011 Feb;3(2):89-96. doi: 10.1002/dta.220. Epub 2010 Dec 29. PMID: 21322119.

11. Singh VM, Browne T, Montgomery J. The Emerging Role of Toxic Adulterants in Street Drugs in the US Illicit Opioid Crisis. Public Health Rep. 2020 Jan;135(1):6-10. doi: 10.1177/0033354919887741. Epub 2019 Nov 18. PMID: 31738861; PMCID: PMC7119254.

12. CDC, Fentanyl Facts