Fatalne skutki chwilowej przyjemności: opis przypadku ostrego uszkodzenia nerek potencjalnie związanego z zażyciem kokainy

■ INTRODUCTION

Cocaine is a natural sympathomimetic alkaloid extracted from coca plant, genus Erythroxylum, cultivated in Central and South America [1].
Except for medical indications, cocaine use is prohibited by law in many countries. However, cocaine is readily and cheaply available on the black market and can be found in two forms. The first being cocaine hydrochloride, commonly called “coke”, “blow” or “Charlie” as a fine white powder administered intranasally, orally or intravenously. The other form is known as “crack cocaine”; it is a free-base form derived from the previously mentioned powder and is mainly smoked and inhaled [2]. Cocaine users claim that cocaine relaxes, alleviates stress and offers a sense of well-being.
Cocaine has been used as a stimulant in South America for more than 5,000 years; it was initially consumed by chewing or brewing tea from the leaves of the coca plant. In 1855, cocaine was first isolated from the plant, which further led to its widespread use. Cocaine was commonly used as an ingredient in various products such as coca wine, Coca-Cola and local anaesthetic treatments [3, 4]. One of the most famous users and defenders of cocaine was Sigmund Freud, the Austrian neurologist. In 1884, he published Über Coca where he analysed its pharmacological properties. Freud experimented with cocaine on himself, noting its pain-relieving, mood-altering and anaesthetic effects. Although initially diagnosed with oral cancer, Freud’s prolonged survival leads to the suggestion that his facial lesions might have been caused by the necrotising effects of cocaine rather than the cancer [5].
Cocaine’s euphoric effects, increased concentration and improved general well-being contri­bute to its high addictive potential. Regular cocaine users, however, may eventually experience negative symptoms like insomnia, restlessness, irritability, dysphoria and impulsive behaviour. However, not many people are aware of the negative physiological effects associated with its toxicity. The negative physical symptoms include hyperthermia, disturbances in vital systems including the cardiovascular, respiratory and urinary systems and brain and liver function [1].
Cocaine-induced kidney damage can manifest as acute and chronic kidney damage or as kidney infarction [6]. Acute kidney injury (AKI) is defined as an increase in creatinine of ≥ 0.3 mg/dl in 48 h or an increase in creatinine 1.5 times in the past 7 days or diuresis of less than 0.5 ml/kg for at least or over 6 hours [7]. To diagnose and determine AKI aetiology, it is necessary examine the patient and their history. It is also important to check serum creatinine level, urine output and creatinine clearance [8]. This article presents a case of AKI caused by cocaine use. The aim of the description was to highlight the consequences of cocaine use and to present the course of treatment with laboratory results.

■ CASE DESCRIPTION

A 23-year-old shipping-company employee was admitted to emergency following a physical assault that had occurred a few hours previously. The patient was reported to have been brutally attacked, having received multiple blunt trauma to the chest, abdomen and head. The patient admitted to being under the influence of cocaine though did not state exactly how much he had taken prior to the incident. At the time of admission, the patient was conscious, in full logical contact and received a score of 15 points on the Glasgow scale. A thoroughly interview revealed the patient had a history of chronic psoriasis treated with the immunosuppressive drug cyclosporine for the past four years. The patient denied he suffered from any other medical conditions. Additionally, when questioned about potential drug or alcohol usage, the patient mentioned occasional marijuana and cocaine intake over recent years as well as regular beer consumption throughout the week.
Physical examination did not reveal any signi­ficant nor life-threatening abnormalities related to the received trauma; however, the Goldflam symptom was symmetrically positive, which indicated possible kidney damage. Various imaging scans like a chest X-ray and full body computed tomo­graphy scan as well as diagnostic blood tests were performed following recommendations.
The results of the imaging scans did not reveal any apparent trauma to the patient’s internal organs nor any brain damage. However, diagnostic tests presented a creatinine level of 2.68 mg/dl and an estimated glomerular filtration rate (eGFR) of 31.6 ml/min/1.73m². According to norms, the value of creatinine for a healthy adult male should not exceed 1.3 mg/dl and eGFR be above 90 ml/min/1.73 m²; both diagnosed blood values were abnormal. Creatinine was significantly elevated whereas the eGFR was notably reduced, indicating potential renal complications due to kidney damage of an unknown aetiology, including potential cocaine use. The unusual test results, posi­tive Goldflam sign and history of cyclosporine treatment suggested inclusion and consideration in the diagnostic process was required.
The patient was therefore referred to the nephrology department for further diagnostic testing and possible treatment. A wide range of tests were performed, including crucial kidney and liver markers, urinalysis, C-reactive protein (CRP), electrolyte levels (so­dium, potassium, calcium), some vitamin le­vels (D₃, B₁₂, folic acid), immunological markers and alcohol and drug tests. The creatinine level increased to 3.62 mg/dl, eGFR further decreased to 22.3 ml/min/1.73 m², and urine drug tests (6-component test) performed in duplicate to rule out false positives, revealed cocaine traces. Although confirmatory tests in the form of blood tests were not performed, this result was consi­dered signi­ficant given the patient’s history and clinical context. Therefore the impact of cocaine use was considered one of the possible causes of acute renal complications. Besides, the patient had persistently high blood pressure values and aspartate aminotransferase (AST) was 57 U/l, while the norm is below 35 U/l. Blood cyclosporine levels were also measured to be within normal limits.
Based on the results of the tests, other potential causes of AKI were excluded. Assessment of the patient’s hydration and normal urine volume and colour eliminated hypovolaemia as a cause of AKI. Sodium, potassium, calcium and vitamin (D₃, B₁₂, folic acid) levels were normal, which elimi­nated metabolic disorders. Urinalysis was normal and renal ultrasound showed no abnormalities, ruling out structural changes. Immunological markers came out negative, excluding a rheumatological origin of the disease. Antinuclear antibodies (ANA), anti-glomerular basement membrane (GMB) anti­bodies, hepatitis C virus (HCV), hepa­titis B virus (HBV) and human immunodeficiency virus (HIV) tests were negative. C3 and C4 complement levels were normal. CRP levels, although initially elevated, gradually decreased, which, combined with the absence of other signs of infection discounted an infectious basis for the kidney injury. The substance ingested by the patient may have been contaminated with other toxic substances. Negative tests for other drugs and toxins (marijuana, morphine, benzodiazepine and amphetamine) that we could detect, in addition to cocaine, ruled out poisoning by other substances. Also cyclosporine blood levels were normal, which ruled out its toxic effects.
Despite limitations in confirming cocaine toxicity to rule out other possible causes with additional tests, the patient’s clinical condition, the known nephrotoxic effects of cocaine, significant deterioration in markers of renal function and the exclusion of other potential causes led to the diagnosis of acute renal failure (AKI) potentially related to cocaine. Subsequently treatment was administered. The patient was treated with allopurinol for high uric acid and was given a dietary supplement that contains L-ornithine L-aspartate and choline because of a high aspartate aminotransferase result. In addition, he received amlodipine (calcium antagonist) due to persistently high blood pressure. Furosemide (loop diuretic) was prescribed to improve diuresis. The patient complained of constant pain, probably related to the trauma so received paracetamol as well as metamizole and drotaverine as analgesics. Furthermore, pantoprazole (a proton pump inhibitor) was administered to premedicate any complications associated with the pain medication received. During the treatment, control tests were performed revealing an improvement in the patient’s kidney condition; however, the blood pH was found to be decreasing and so fluids like PWE, 0.9% NaCl and sodium bicarbonate were administered. Furthermore, during the patient’s stay at the hospital, he was found to be in a constant state of unrest with insomnia and so also received a sedative mix. Apart from the treatment of the patient’s current medical complications, treatment of his chronic psoriasis was continued with cyclosporine.
During the treatment period, the patient received regular blood tests. A positive reaction to the treatment was observed, and this is shown in Table I, as the creatinine levels fell from the initial 2.68 mg/dl to 1.24 mg/dl within one and a half weeks of treatment. The decrease in creatinine levels was also accompanied by a substantial, three-fold increase in the eGFR from 31.60 ml/min/1.73 m² to 76.8 ml/min/1.73 m². The positive response to treatment indicates that, despite it being difficult to make a clear diagnosis, the treatment process was well suited to the patient’s condition. This was also apparent from the patient’s good physical condition, which allowed him to be discharged from the nephrology department. On discharge, the patient was advised to revisit the nephrology department to monitor and maintain his renal health in the long-term. However, despite the recommendations, the patient has not attended the scheduled consultations, which underscore the challenges of ensuring continuous care.

■ COMMENTARY

Cocaine acts by blocking voltage-gated sodium channels, preventing sodium from entering cells, which inhibits depolarisation and stops electrical impulses. Its psychoactive and sympathomimetic effects also stem from blocking the reuptake of serotonin, noradrenaline and dopamine. In addition, there is excessive activation of the renin-angiotensin-aldosterone system and accelerated atherogenesis, both of which lead to fibrosis. Organ haemodynamics and structure are also impaired by constricted blood vessels [1, 9].
The pathophysiology of cocaine’s effects on the kidneys is not yet fully understood, but it is already known to be a complex process influenced by changes in renal haemodynamics, glomerular matrix synthesis and degradation processes, oxidative stress and the development of renal atherosclerosis. These mechanisms can lead to a variety of kidney problems, such as chronic glomerulonephritis, interstitial nephritis and, as in the case we described, AKI [9]. It is also important to note the association of rhabdomyolysis with AKI in most patients after cocaine use. This is most likely due to factors like the muscle toxicity of cocaine, disseminated intravascular coagulation or ischaemia. The vast minority of cases of AKI with cocaine use proceed without rhabdomyolysis [10].
Diagnosis of AKI is not unproblematic, although serum creatinine levels can be readily obtained; however, there are many factors like age, gender and muscle mass that affect its concentration [8]. It is also known that serum creati­nine changes are not highly sensitive indicators of AKI because approximately 50% of glomerular filtration rate (GFR) must be lost in a healthy individual before there is a detectable change in serum creatinine [7]. When it comes to urine output, errors in collection and documentation are high likely. In turn, creatinine clearance directly measures GFR and provides a more accurate assessment of renal function than serum creatinine. Other useful tests in the diagnosis of AKI are urinalysis, urine micro­scopy, urine electrolytes, renal USG and renal biopsy [8]. The creatinine level as well as eGFR were abnormal in the patient from the presented case. On the other hand, the abdominal USG showed no abnormalities.
There is no specific treatment for AKI. The focus should be on monitoring the patient’s hydration status and vital signs. Fluid resuscitation, isotonic crystalloids like lactated Ringer’s solution or 0.9% normal saline are recommended. It is important to remember that there is a delicate balance between optimising renal perfusion and avoiding fluid overload. The goal is to achieve a mean arterial pressure of 65 mmHg or higher. If this cannot be achieved with fluid resuscitation alone, vasopressor medications must be used. It is also important to avoid nephrotoxic medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), aminoglycosides, allopurinol, angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors in time of AKI [8].
It is worth emphasising that patients who have undergone AKI should present for follow-up exa­minations in a timely manner. The described patient never attended the recommended follow-up visit after discharge from hospital, making it impossible to assess his full recovery. Jill Vanmassenhove and his colleagues suggest an algorithm for renal follow-up after AKI in high risk patients. It is reasonable to schedule a follow-up three months after hospitalisation if renal function has returned to at least 90% of baseline. For those with slower recovery, there should be a follow-up at three weeks and then again after three months. At each visit, blood pressure, weight, serum creatinine and GFR should be monitored [11].
The full pathophysiology of why kidney damage occurs is still unknown, and research should be urgently conducted to gain a better understanding of the mechanisms involved. This could allow for better and more effective diagnosis and treatment of patients with AKI caused by cocaine damage. It is also important to stress how difficult it is to treat cocaine-induced AKI. Due to the lack of specific treatment and the need for follow-up visits, there can be complications like chronic kidney disease. In order to prevent this, it is also necessary to increase patient education on the side-effects of drugs, which would reduce subsequent complications. The temporary relaxation after cocaine use is not worth the great risk of serious medical complications.

Conflict of interest/Konflikt interesów

None declared./Nie występuje.

Financial support/Finansowanie

None declared./Nie zadeklarowano.

Ethics/Etyka

The work described in this article has been carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) on medical research involving human subjects, Uniform Requirements for manuscripts submitted to biomedical journals and the ethical principles defined in the Farmington Consensus of 1997.
Treści przedstawione w pracy są zgodne z zasadami Deklaracji Helsińskiej odnoszącymi się do badań z udziałem ludzi, ujednoliconymi wymaganiami dla czasopism biomedycznych oraz z zasadami etycznymi określonymi w Porozumieniu z Farmington w 1997 roku.

References/Piśmiennictwo