The necessary pathway for metabolic and crystallographic analysis of kidney stones: struvite may not differ from its counterparts

Struvite stones represent the most common cause of the rapidly growing staghorn calculi whose predisposing factors include female sex, stasis from urinary tract malformations or obstruction, neurogenic bladder, among others¹. Their relevant morbidity is ascribed to the frequent association with recurrent urinary tract infections (UTI), pyelonephritis, perinephric abscess or even sepsis, not to mention the potential loss of renal function². Moreover, lower social economic status and poor health care quality are closely related to reduced access to procedures for stone removal, lower rates of preventive management, and delayed or no treatment of recurrent UTI, altogether predisposing to the formation of infection stones. Accordingly, Cunha et al.² have recently shown that struvite calculi are most commonly observed in areas of low human development indexes (HDI). As a consequence, patients may undergo radical nephrectomy more frequently compared to patients with other type of stones. Finally, there seems to be a greater chance of progressive renal dysfunction or chronic kidney disease (CKD) as a result of nephrectomy among struvite stone-forming patients, obstructive uropathy, or recurrent UTI³.

We read with great interest the work of Danilovic et al⁴, who conducted a retrospective evaluation of the charts of patients submitted to unilateral total nephrectomy due to pure MAP (magnesium ammonium phosphate or struvite stones) or pure calcium oxalate (CaOx) stones, searching for urinary metabolic parameters predictive of new clinical events. Although this topic has been raised in recent years¹, the lack of data in our population highlights the epidemiologic relevance of their study⁴.

The authors found a similar frequency of metabolic abnormalities in 24-hour urine tests between groups, but only important for hypocitraturia. There was no significant difference in new events between groups, and treatment of metabolic abnormalities among patients with MAP stones rendered them prone to the same risk for a new event as those without any metabolic disturbance.

Although metabolic abnormalities in pure struvite stone formers indeed appear to be more common than previously reported, the profile of metabolic alterations differ among reports. Iqbal et al¹, for instance, reported much higher rates of hypercalciuria (43%) and lower rates of hypocitraturia (14%) among pure struvite stone formers than the ones presented by Danilovic et al⁴. A possible reason could have been a sample with approximately a third of patients in stage 3 CKD in both groups (CaOx and MAP) by the latter. Moreover, there are limitations in urinary metabolic evaluation of patients with glomerular filtration rates (GFR) lower than 60 mL/min/1.73m², especially concerning lower rates of urinary calcium, due to secondary hyperparathyroidism, as already demonstrated in primary struvite urolithiasis populations⁵. The authors also did not find differences in citrate excretion between MAP and CaOx groups although urinary citrate has been shown to correlate with eGFR⁶. Therefore, the metabolic evaluation in this group of patients must be interpreted with caution. Although potassium citrate supplementation may help prevent struvite crystallization, overt alkalinization must be averted. Due to the retrospective characteristic of the study, urinary pH values were unfortunately not available before or after nephrectomy. Another concern highlighted by the authors was the chemical analysis of the calculi, which might have hampered their analysis, providing inaccurate reporting of mineral composition. Kidney stones should preferably be analyzed by a physical method, namely a crystallographic analysis, typically performed by either infrared spectroscopy (IRS) or X-ray diffraction (XRD) to better identify mineral types and even distinguish between brushite from other forms of calcium phosphate or pure MAP⁷.

Nevertheless, the study by Danilovic et al⁴ sheds light on the management of kidney stones in the ambulatory setting. One should consider frequent evaluation of the medical history and physical examination, stone analysis by XRD or IRS in different time frames, and periodic metabolic evaluation based on 24-h urine samples⁵ especially in cases that need surgical procedures and in patients with altered clinical manifestations and social or geographic changes in the time course of follow up, as these factors may affect management overtime.

References

• ¹
  Iqbal MW, Shin RH, Youssef RF, Kaplan AG, Cabrera FJ, Hanna J, et al. Should metabolic evaluation be performed in patients with struvite stones?. Urolithiasis. 2017 Apr;45(2):185-92. DOI: https://doi.org/10.1007/s00240-016-0893-6
  » https://doi.org/10.1007/s00240-016-0893-6
• ²
  Cunha TDS, Rodriguez A, Heilberg IP. Influence of socioeconomic disparities, temperature and humidity in kidney stone composition. Braz J Nefrol. 2020 Oct/Dec;42(4):454-60. DOI: https://doi.org/10.1590/2175-8239-JBN-2019-0206
  » https://doi.org/10.1590/2175-8239-JBN-2019-0206
• ³
  Carvalho M, Martin RLS, Passos RC, Riella MC. Nephrectomy as a cause of chronic kidney disease in the treatment of urolithiasis: a case-control study. World J Urol. 2013 Oct;31(5):1141-5. DOI: https://doi.org/10.1007/s00345-012-0845-x
  » https://doi.org/10.1007/s00345-012-0845-x
• ⁴
  Danilovic A, Ferreira TAC, Gomes SA, Wei IA, Vicentini FC, Torricelli FCM, et al. Metabolic assessment in pure struvite stones formers: is it necessary?. Braz J Nephrol. 2021 Apr 29; [Epub ahead of print]. DOI: https://doi.org/10.1590/2175-8239-jbn-2020-0106
  » https://doi.org/10.1590/2175-8239-jbn-2020-0106
• ⁵
  Kristensen C, Parks JH, Lindheimer M, Coe FL. Reduced glomerular filtration rate and hypercalciuria in primary struvite nephrolithiasis. Kidney Int. 1987 Nov;32(5):749-53. DOI: https://doi.org/10.1038/ki.1987.270
  » https://doi.org/10.1038/ki.1987.270
• ⁶
  Goraya N, Simoni J, Sager LN, Madias NE, Wesson DE. Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis. Kidney Int. 2019 May;95(5):1190-6. DOI: https://doi.org/10.1016/j.kint.2018.11.033
  » https://doi.org/10.1016/j.kint.2018.11.033
• ⁷
  Williams Junior JC, Gambaro G, Rodgers A, Asplin J, Bonny O, Costa-Bauzá A, et al. Urine and stone analysis for the investigation of the renal stone former: a consensus conference. Urolithiasis. 2021 Feb;49(1):1-16. DOI: https://doi.org/10.1007/s00240-020-01217-3
  » https://doi.org/10.1007/s00240-020-01217-3

Publication Dates

• Publication in this collection
  24 May 2021
• Date of issue
  Apr-Jun 2021

History

• Received
  06 Apr 2021
• Accepted
  14 Apr 2021