Renal Effects of Meth

Methamphetamine is primarily metabolized in the liver and excreted by the kidneys. The kidney is most commonly affected by methamphetamine use. In 2020, Isoardi et al. looked at patients with self reports drug use and found of the 595 patients presenting to the emergency department:

• 73 had elevated creatinine with a median concentration of 125 μmol/L, with 90% of the cases meeting diagnostic criteria for Acute Kidney Injury.
• 44% of cases had concurrent rhabdomyolysis, with a median creatine kinase level of 2695.

Methamphetamine overdose commonly causes renal dysfunction and can cause multisystem organ failure.

Pillai et al. (2019) case report discussed a 27-year-old male that ingested approximately 1.5 grams of methamphetamine. When he arrived in the ED, he had a Glasgow coma scale (GCS) score of 3T and was reported to have a heart rate of 200/min is sinus tachycardia on the monitor. His respirations at 40/min, and he was hypotensive -systolic blood pressure in the 60s. His muscles were rigid, and his core body temperature was 42.2 °C (108 °F).

The patient’s urine was positive for meth and experienced respiratory acidosis, hyperkalemia, AKI, and elevated CK levels. The patient experienced hypotension, hyperthermia, and rhabdomyolysis, eventually progressing to disseminated intravascular coagulation and multiorgan failure. The patient died in the ICU after hours of supportive care.

The effects of methamphetamine on the kidneys can be divided into three sub-groups: vascular effects, nontraumatic rhabdomyolysis, and direct nephrotoxicity

Vascular effects, methamphetamine indirectly increases blood pressure by constriction of blood vessels. Amphetamine and methamphetamine vasoconstriction induced ischemia and hypoxia can prompt progressive necrotizing vasculitis in different organs, including renal and gastrointestinal systems (Godrati, 2020).

• A study by Seo, et al. (2016) demonstrated the vasoconstrictive effects of methamphetamine are due to the release of endothelin-1 (ET-1) from vascular endothelial cells; and that ET-1 is the most powerful vasoconstrictor (100-times more potent than noradrenaline).
• Kohan, et al. (2011) reported that the production of ET-1 by the kidney is much higher than any other organ.
• Jaffe and Kimmel (2006) demonstrated, increased production of ET-1 caused decreased renal blood flow and glomerular filtration rate (GFR) and consequently induces renal hypertension.
• Schneider, et at. (2002) reported that in diabetic and hypertensive patients, plasma ET-1 concentrations can be increased several times compared to normal healthy individuals.
• Two key findings of the renal effects of ET-1:
  • the adjustment of renal hemodynamics associated with its vascular activity
  • renal hemodynamic changes cause variation of water and sodium secretion through ET-1 action on tubular cells (Godrati, 2020).

Nontraumatic rhabdomyolysis caused by the myotoxic effects of methamphetamine results in increased level of plasma myoglobin. Released myoglobin damages and reduces the function of filtration in kidneys resulting in acute kidney injury or renal failure.

In addition, secretion of myoglobin causes increase concentrations of plasma ET-1. It is concluded that E-1is at least partially, contributing to the significant tubular cell injury detected in myoglobinuric nephropathy (Karam, 1995).

References

Darke S, Duflou J, Kaye S. (2017)Prevalence and nature of cardiovascular disease in methamphetamine-related death: A national study. Drug Alcohol Depend. 2017;179:174-179. doi:10.1016/j.drugalcdep.2017.07.001

Godrati, S., Pezeshgi, A., Valizadeh, R., James Kellner, S., & Radfar, S. R. (2019). Acute and delayed nephropathy due to methamphetamine abuse. Journal of Nephropathology, 9(3). https://doi.org/10.34172/jnp.2020.22

Isoardi KZ, Mudge DW, Harris K, Dimeski G, Buckley NA. Methamphetamine intoxication and acute kidney injury: A prospective observational case series. Nephrol Carlton Vic. 2020;25(10):758-764. doi:10.1111/nep.13762

Jaffe JA, Kimmel PL. Chronic nephropathies of cocaine and heroin abuse: a critical review. Clin J Am Soc Nephrol. 2006; 1:655-67. doi: 10.2215/CJN.00300106.

Karam H, Bruneval P, Clozel JP, Löffler BM, Bariéty J, Clozel M. (1995). Role of endothelin in acute renal failure due to rhabdomyolysis in rats. J Pharmacol Exp Ther. 274:481-6.

Kohan DE, Inscho EW, Wesson D, Pollock DM. Physiology of endothelin and the kidney. Compr Physiol. 2011;1:883- 919. doi: 10.1002/cphy.c100039.

Pillai, S., Cesarz, B., Boulware, C., & Khan, A. (2019). Hypotension, Severe Hyperthermia (42°C), Rhabdomyolysis, and Disseminated Intravascular Coagulation Induced by Lethal Dose of Methamphetamine. Cureus, 11(7), e5245. https://doi.org/10.7759/cureus.5245

Schneider JG, Tilly N, Hierl T, Sommer U, Hamann A, Dugi K, et al. Elevated plasma endothelin-1 levels in diabetes mellitus. Am J Hypertens. 2002;15:967-72.

Seo JW, Jones SM, Hostetter TA, Iliff JJ, West GA. Methamphetamine induces the release of endothelin. J Neurosci Res. 2016;94:170-8. doi: 10.1002/jnr.23697.