Kidney Injury Associated with Cocaine Use

Cocaine consumption has multi-systemic consequences such as renal insufficiency, hepatotoxicity, and lung toxicity. Acute and chronic renal changes are induced by consumption. This study aimed at reporting two cases of acute renal damage with different diagnoses related to cocaine use.


Introduction
A prothrombotic effect is recognized by increasing platelet aggregation and adhesion and reducing the activity of prostacyclin E2 [4]. It raises body temperature due to an increase in muscle activity, vasoconstrictive heat loss, and hypothalamic temperature control loss due to the depletion of dopamine receptors. All the systemic effects described are responsible for the complications on the different systems with deleterious effects both in the short and longterm [5] (Table 1). Specifically, renal involvement is often considered, although less frequently, mediated by rhabdomyolysis; nonetheless, it was also described that renal involvement was directly associated with vasculitis, direct tubulointerstitial injury, and glomerular vasoconstriction [6]. In this document we describe two clinical cases of acute kidney injury associated with cocaine use, we present their clinical characteristics and we will briefly review the literature on this topic.

Discussion
Cocaine is known to affect all components of kidney tissue and the pathophysiological mechanisms involved in toxicity are multiple [6]. Cocaine-induced rhabdomyolysis caused by of acute renal failure was the first to be described in the medical records, the suggested mechanisms are ischemia, direct cellular injury due to increased production of oxygen free radicals production, vasoconstriction, and the myoglobin crystals produced by cocaine-induced muscle necrosis [7]. Some researchers reported ANCA-associated which might be related to the consumption of substances used to adulterate cocaine such as levamisole or alcohol used for cooking it (toxic metabolites) or those that increase the psychostimulant effect, which is a regular practice in recreational consumers [8]. Acute renal infarction is another mechanism described [9]. In the clinical case, 1 we describe the usual form of presentation of acute renal infarction with lumbar pain and hematuria, in a patient with a clear record of cocaine use, it could be the reason. There was no alteration of renal function, in this case, due to unilateral renal involvement. Anuria and complete renal failure with the requirement for renal support have been described in cases of bilateral renal involvement, however, it is an even rarer form of presentation [10]. right renal involvement agrees with that some researchers described and it is estimated that it is due to a bigger size of the renal artery and a multiplied resistance to flow, which might be related to microthrombus formation.
Data from observational studies and multiple case reports show the association of cocaine consumption with cardiac and cerebral thrombosis, suggesting that cocaine itself has a marked prothrombotic effect [11]. At the renal level, the mechanisms of the genesis of the renal infarction described are based on observational studies and animal models that seem to involve a combination of marked vasoconstriction due to an increase in circulating catecholamines, elevated levels of endothelin 1, and micro thrombosis due to alteration of platelet aggregation and an increase in thromboxane synthesis as well as alteration of intrarenal hemodynamics by a mechanism that is not clear [10,11].
There is no established treatment for renal thrombosis associated with cocaine use and in the clinical case that we describe, since there was no alteration in renal function, its evolution was favorable only with established support measures. In Clinical case number 2, we describe a middle-aged man with a record of severe renal failure and accelerated hypertension in cocaine users, the mechanisms are not fully recognized, they could be related to the combination of platelet microthrombus formation and direct endothelial damage due to severe hypertension that characteristic of this condition [11,12]. No immunity alterations were described in cocaine use, in contrast with other [0] secondary causes of drug-related thrombotic microangiopathy Although the prevalence of MIT is higher in women, the descriptions made in cocaine users place it predominantly in men, due to its higher consumption in this age group [13] (Diagram 1). Regarding the histological findings reported in our study, it can be verified that they belong to those usually described in thrombotic microangiopathies with renal involvement (notorious fibrinoid necrosis of the capillary tufts and glomerular arterioles) and that they reflect the renal tissue response to injury due to ischemia; [14] however, although the pathological findings mentioned in the recently described COVID 19 infection are multiple and affect all components of the renal tissue, the latter is associated with a predominantly tubulointerstitial and glomerular inflammatory involvement that is less common in patients with secondary thrombotic microangiopathies.

Diagram 1:
Proposed pathophysiological mechanisms of renal injury induced by cocaine and/or its metabolites. MAT: Thrombotic Microangiopathy; RAAS: Renin-Angiotensin-Aldosterone System. Cocaine causes acute kidney injury by two mechanisms:

1)
Indirectly After muscle injury, rhabdomyolysis occurs (the most frequent mechanism) and 2) Directly: Cocaine or its metabolites could induce direct injury by vasculitis, micro thrombosis formation, renal infarction, hypertensive nephropathy. Repeated episodes of acute kidney injury by mechanisms previously described would lead to the development of chronic kidney disease.
without acute renal failure. The second case with cocaine-induced acute kidney injury without rhabdomyolysis or ischemic or toxininduced acute tubular necrosis. Renal failure with malignant hypertension was the main clinical manifestation in this patient.
The histological characteristics were compatible with thrombotic microangiopathy. The mechanisms responsible for these pathological changes are unclear but are most likely multifactorial.
Diffuse endothelial vascular injury due to direct toxicity or cocaineenhanced catecholamine release is likely a major contributor factor to the renal pathology observed in the 2 reported cases. Due to the diversity in the pathophysiological mechanisms involved in kidney damage, the final diagnosis usually requires a histopathological study; however, the importance of a comprehensive approach is highlighted, considering the possibilities in the differential diagnosis of acute kidney injury, particularly in young patients.