Recurrent urinary tract infections in a 48-year-old female.
Urolithiasis, which encompasses calculi anywhere within the renal calyces, ureters or bladder, is a common problem encountered by both the primary care clinician and by the pathologist. In the Unites States alone nearly 2 million annual outpatient visits are attributed to urolithiasis symptomatology; and the prevalence appears to be rising from roughly 4% in the late 1970s to nearly 8.5% in the period from 2007 to 2010. (1) Though the reasons for the apparent increase in frequency are largely unknown, risk factors for stone development have long been understood. These include a strong association with diabetes as well as a higher incidence in those with obesity, a low fluid intake, and high dietary salt. For patients with chronic or recurrent urinary tract infections (UTIs), particularly those due to Proteus, the risk for the staghorn or struvite form of stone, as seen in this case, is specifically higher. In addition, men are two fold more likely to develop nephrolithiasis than women and first degree relatives of those with urinary stones are also at greater risk. The peak age in men is 30 years; but women have a bimodal age distribution with peaks at 35 and 55 years. (2) Certain anatomical abnormalities of the urinary tract and specific drugs can increase the chances of stone formation; and, finally, there are several inherited disorders predisposing individuals metabolically to nephrolithiasis such as autosomal recessive cystinuria and X-linked recessive Lesch-Nyhan syndrome. (1-3)
Stone analysis to determine chemical composition is an important aspect in the recommended management algorithm for patients with kidney stones. First reported at the end of the 18th century, chemical composition of urinary calculi has long been known but now is being utilized to drive not only treatment decisions but also later recommendations for prevention of recurrences. (4,5) Kidney stones are composed of crystalline and non-crystalline materials. The frequency of the more common crystalline constituents can be seen in Table 1 though some stones are actually mixtures of two or more compounds. The most frequent individual crystalline component is calcium oxalate (70-80%), though up to 50% of these can also include calcium phosphate either in the apatite or brushite form. Another 15% are the struvite stone that form only in the presence of the urease-producing bacteria such as Proteus mirabilis, Klebsiella, Serratia and Mycoplasma in the upper urinary tract like the calyces or proximal ureter. (2) If singular, this stone is often multifaceted and large--said to be staghorn in shape; but often it can be multiple stones that fragment to fill up and conform to the shape of the renal calyceal system. The multifocality of a typical struvite stone is well depicted by the current case and seen above in Figure 1. The struvite stone is also known as the triple phosphate or magnesium ammonium phosphate stone as well as the 'infection stone' given its strong association with recurrent UTIs and an alkaline pH urine. This association with urinary infections also explains the struvite stone's relatively greater frequency in women, unlike the typical urinary stones. (3,5) Subsequent chemical analysis in the current case later confirmed the stone to be struvite in composition.
As the interpretation of kidney stone analysis has certain impact on the treatment modality that is selected for the patient, both the treating physician and the laboratory pathologist need to have an awareness of its importance. Although a 24-hour urine composition study may provide clues as to the potential composition of a patient's stone, it is not a fully predictive or reliable approach; and actual analysis of a passed or retrieved stone specimen is preferable. The calculus can be submitted to the pathology laboratory fresh, in a clean dry container without any fixative solution, and stone analysis can be requested. If a gross specimen such as a nephrectomy specimen is received to the surgical pathology lab, as was the situation in this case, the pathologist can extract one or more stones and submit the stone for subsequent chemical analysis. A later statement should be issued on the pathology report about the chemical composition once it is resulted. Once in the laboratory, chemical analysis may be performed on the calculus using a variety of methods with wet chemical analysis being the most widely used approach but infrared spectroscopy considered as the gold standard. (4)
The current recommendations for chemical analysis include one stone analysis in every urolithiasis patient. Given the frequency of recurrences which averages 5% per year (1) and the fact that some patients produce more than one stone type, a second stone analysis for a patient is reasonable. One study found a 25% discordance rate between stone composition in patients who had bilateral nephrolithiasis. Most algorithms follow that once two analyses show sufficiently similar stone constituents; no further chemical analysis is warranted in future recurrences. (5,6)
Though the overall prognosis for patients with urolithiasis is quite good, the associated morbidity and, in particular, the associated pain can be quite debilitating. Though 80-85% of stones, especially those under 5mm in diameter, pass spontaneously, another 10-20% will require radiologic or surgical intervention for removal. In either case, awareness about the need for retaining the calculus for subsequent lab study is important and may require patient education. (2) The usually quoted recurrence rate for urolithiasis is approximately 15% at 1 year, 35-40% at 5 years and 50% at 10 years with men being more likely to recur than women. (1) In those with recurrent stone formation, there is a risk for the development of renal failure albeit low at 3%,4 but the most dangerous aspect of stone disease is the combination of urinary tract obstruction and upper UTI that can ultimately lead to pyelonephritis and urosepsis. (1)
The case depicted here illustrates the typical struvite form of urolithiasis in a female patient with known Proteus UTIs. Though fortunately there was no progression to acute pyelonephritis or urosepsis, ultimately a nuclear radioisotope renography confirmed the right kidney, affected by the nephrolithiasis, to be essentially nonfunctional; thus resulting in the recommendation for a unilateral nephrectomy, which was performed without complication. Retrospective questioning also revealed a family history of urolithiasis in multiple family members thus calling into question a familial predisposition to stone formation. Further comorbities placing the patient at higher risk included diabetes, hypertension and obesity. Chemical analysis was properly pursued at the time of nephrectomy by the treating physician and the pathologist on this case and, given the struvite stone composition, future management was planned with an eye towards long term UTI prevention. To date, six months' post nephrectomy there remains complete resolution of urinary symptoms.
Acknowledgements: The authors gratefully acknowledge the support of University Medical Center New Orleans for providing the case material for this report.
(1.) Tan JA and Lerma EV. Nephrolithiasis for the primary care physician. Diseasea-Month. 2015; 61: 434-41.
(2.) Parmar M. Clinical Review: Kidney stones. Brit Med J. 2004; 328:1420-4.
(3.) Aggarwak K, Narula S, Kakkar M, et al. Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators. J Biomed Tech. 2013; 1-21.
(4.) Basiri A, Taheri M, and Taheri F. What is the State of the Stone Analysis Techniques in Urolithasis? Urol J. 2012; 9(2):445-54.
(5.) Curhan, Gary C. "Interpretation of Kidney Stone Analysis." Interpretation of Kidney Stone Analysis. Wolters Kluwer, 20 Oct. 2015. Web. 01 Apr. 2016.
(6.) Kadlec AO, Fridirici ZC, Acosta-Miranda AM, et al. Bilateral urinary calculi with discordant stone composition. World J Urol. 2014; 32(1):281.
In the Department of Pathology at Louisiana State University School of Medicine in New Orleans: Dr. Connor is a third year pathology resident, Dr. Vinson is a first year pathology resident, Dr. Bhalla is an Assistant Professor of Pathology and Dr. McGoey is an Associate Professor of Pathology and Residency Program Director.
Table 1: Summary of the common crystalline components in urinary calculi including their incidence and the factors that influence their development. Medical therapy is directed at reversing these factors. Chemical Composition Frequency Causative Factors Calcium-containing 70-80% Underlying metabolic abnormality (hypercalciuria, hyperoxaluria, decreased urinary citrate excretion) Struvite 10-20% Urease producing bacteria (infection) Alkaline pH Urate 5% Hyperuricemia Acidic pH Cystine 1-2% Renal tubular defects
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|Title Annotation:||PATHOLOGY IMAGE OF THE MONTH|
|Author:||Connor, Ellen E.; Vinson, Anthony; Bhalla, Ritu; McGoey, Robin R.|
|Publication:||The Journal of the Louisiana State Medical Society|
|Article Type:||Clinical report|
|Date:||Mar 1, 2016|
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