Alkaline-Encrusted Pyelitis Causing Renal Failure in a Transplant Kidney: Treatment with Percutaneous Nephrolithotomy and Urinary Acidification

Abstract

Background: Alkaline-encrusted pyelitis (AEP) is rare and most often stems from a triad of immunodeficiency, urogenital tract trauma, and alkaline urinary infection. Corynebacterium Group D2 is the most common organism. It results in encrusting calcifications that adhere to most of the urothelial lining of the pelvicaliceal system and ureter. Left unchecked, or unrecognized, the disease process can progress to renal compromise. Studies suggest that management is based on elimination of the bacterium, acidification of the urine, and elimination of calcified plaques and encrustations. Herein, we report a case of a 56-year-old woman who developed AEP in her second transplanted kidney, and detail the diagnosis and treatment of the uncommon, yet potentially devastating, disease.

Case Presentation: A 56-year-old woman with a history of lupus, end-stage renal disease, who was on her second renal transplant presented with symptoms of urinary tract infection. Urine was consistently alkaline with cultures repeatedly growing urease-splitting Corynebacterium. Subsequent imaging showed large obstructing ureteral and renal stones concerning for AEP. She was treated with transplant kidney percutaneous nephrolithotomy, culture-specific antibiotics, and urinary acidification.

Conclusion: Clinical presentation, urinalysis, culture, and renal imaging, often with CT, are the mainstays for diagnosing AEP. If not addressed, AEP can advance to renal failure. Management often includes a multimodal approach involving treatment and prevention of the underlying infection, urinary acidification, and percutaneous or endoscopic removal of obstructing and large burden stones and encrustation.

Introduction and Background

Alkaline-encrusted pyelitis (AEP) results in encrustations along the urothelium and can progress to a loss of renal function.¹ Rare reports of AEP have been described with a prevalence of 0.2%.¹ This is believed to be a result of strict conditions necessary to potentiate the development of AEP. Predisposing factors include immunocompromise, urogenital tract trauma, and the presence of a urease splitting bacteria such as Corynebacterium with resultant alkaline urine.² The alkalization leads to the precipitation of solutes resulting in stone formation. Kidney transplant recipients are at increased susceptibility because of chronic inflammatory disease and exposure to nosocomial infections.³ We report a rare case of AEP in an immunocompromised patient who presented with a staghorn calculus and large, completely obstructing ureteral stone within a transplant kidney.

Presentation of Case

A 56-year-old woman with a past medical history of autoimmune lupus erythematosus, end-stage renal disease, and a complex urologic history presented to emergency services complaining of dysuria and hematuria in January 2020. She had a history of native left nephrectomy with subsequent living-related kidney transplantation in 2002. The transplanted graft remained viable until 2014, and thereafter she was transitioned to peritoneal dialysis. In 2019, she underwent a deceased donor kidney transplant and peritoneal dialysis catheter removal.

On initial presentation her urine analysis was significant for pH of 9.0, positive nitrite, and leukocyte esterase. Creatinine was elevated to 3.01 up from baseline of 1.12. Ultrasonography of transplanted kidney demonstrated moderate hydronephrosis, coarse calcifications within the urothelial wall of the pelvocaliceal system and proximal ureter, and multiple large renal calculi suggestive of AEP (Fig. 1). She was admitted, received broad spectrum antibiotics, and underwent transplant nephrostomy tube placement. Urine culture was significant for Corynebacterium; however, she was not given antibiotics on discharge as she was treated with 5 days of cefepime while inpatient. Creatinine improved to 1.8, she was discharged home with vitamin C for urinary alkalization.

FIG. 1.

Kidney ultrasonography demonstrating moderate hydronephrosis with coarse calcifications within the urothelial wall of a calices, pelvis, and proximal ureter.

Follow-up CT demonstrated transplant kidney with persistent hydronephrosis, large calcifications within the proximal ureter, calcification within the lower pole, and peripheral calcifications within cystic structures of the upper pole of the transplanted kidney (Fig. 2). Review of prior urine cultures showed recurrent Corynebacterium infections with urine pH consistently between 7 and 9.

FIG. 2.

Coronal image demonstrating transplant kidney (arrow) with hydronephrosis and large calcifications within the proximal ureter measuring 1.1 × 3.0 cm, and peripheral calcifications lining the urothelium in the upper pole and renal pelvis.

Once optimized, patient underwent percutaneous nephrolithotomy of the transplanted kidney. Intraoperative findings included upper and lower pole renal calculi with adherent encrusting debris of most of the urothelium, complete obstruction of the proximal transplanted ureter was found secondary to encrusting debris that was densely adherent to the urothelial wall. After clearance of the obstructing ureteral stone and encrustation, a ureteral stricture was encountered at the distal edge of the ureteral stone and encrustation. Nephroureteral stent was placed across the strictured segment. Follow-up imaging showed ureteral stone clearance and significant reduction in stone burden and encrustation of the pelvocaliceal system. Patient was placed on linezolid at the recommendation of the infectious disease team and urinary acidification was achieved with vitamin C 1 g p.o. b.i.d., she was discharged on postoperative day 1.

On follow-up stone analysis demonstrated 60% carbonate apatite, 30% ammonium urate, 10% ammonium–magnesium phosphate hexahydrate, urine pH was 6.5, creatinine downtrended to 1.26. Intraoperative stone culture was significant for Corynebacterium. After 4 weeks, nephroureteral stent was converted to a nephrostomy tube once antegrade nephrostogram confirmed ureteral patency and good antegrade flow of contrast into the bladder. A few weeks later, repeat antegrade nephrostogram confirmed continued patency of the ureter with antegrade flow into the bladder (Fig. 3). Thereafter, the nephrostomy tube was removed and repeat laboratories and imaging at 6 months postoperatively showed stable renal function and no signs of repeat AEP or worsening residual hydronephrosis.

FIG. 3.

Antegrade nephrostogram before nephrostomy tube removal, showing ureteral patency and antegrade flow of contrast into bladder. Additional central pelvic calcifications noted in fibroid uterus.

Discussion and Literature Review

Incidence and detection of AEP is rare as it requires specific predisposing factors such as immunosuppression, urea-splitting bacteria to alkalinize the urine, and preceding urologic procedure or mucosal lesion.² Kidney transplant patients are at increased risk as they meet the aforementioned factors, and a handful of cases of AEP has been documented in this population.¹ Patients with can present with nonspecific symptoms such as gross hematuria, flank pain, and fevers.² Urine may demonstrate mucus, purulence, or blood with a characteristically strong scent of ammonia.⁴ Although these are nonspecific findings, AEP should be considered in patients with renal transplants and or in those patients with predisposing risk factors.

AEP is commonly caused by Corynebacterium, which is a slow-growing gram-positive bacillus, and frequently found to have many antibiotic resistances.⁴ Specifically, corynebacterium group D2 organism is the most common bacterium associated with AEP, it is rare and isolated on urine culture with a rate of about 2%, which much of the low culture rate owing to its slow-growing nature.⁴ Adequate culturing often requires ∼72 hours of incubation, and thus urine specimens routinely discarded within 24 hours of collection may lead to false negative culture results.¹

Corynebacterium is urease splitting that leads to the formation of ammonia and alkaline urine. Increase in pH favors precipitation of ammonium (NH₄⁺) with magnesium and phosphate leading to the formation of the classic struvite stone.² NH₄⁺ also allows for the precipitation of carbonate with phosphate leading to the formation of carbapatite; carbonate apatite, ammonium urate, and ammonium–magnesium phosphate hexahydrate that have been shown to be the most common encrustation material associated with encrusting pyelitis.¹

Ultrasonography of AEP demonstrates thickening and calcifications of the bladder wall and dilation and thickening of the upper urinary tract.² Hydronephrosis is also a common finding. CT serves as the confirmatory test.¹ CT demonstrates calcification along the lining of the urinary tract, and is associated with findings of edema and hydronephrosis. CT can lead to early diagnosis and is often considered the mainstay of imaging for renal transplant patients with believed or confirmed AEP.¹ On endoscopic observation, the urothelium often demonstrates marked inflammation throughout the renal collecting system, with ulcerations and whitish plaques corresponding to the underlining calcifications.¹ The plaques are often strongly adherent to the underlying urothelium.

Treatment protocol can be broken down into three categories: elimination of the bacterium, acidification of the urine, and elimination of encrustations.² Corynebacterium has shown increased resistance to antimicrobials commonly used in the treatment of urinary tract infections such as ampicillin, cephalosporins, and fluoroquinolones with resistance rate cited as high as 55%.⁴ Corynebacterium has shown sensitivity to glycopeptides, vancomycin, and teicoplanin. Thus, first-line treatment are glycopeptides, such as linezolid, because of their ability to function regardless of urine pH allowing management of bacterial load throughout the course of the infection.¹ Although there is no set duration of antibiotic usage, most studies suggest that a 2-week course is frequently sufficient for treatment.¹

Urinary acidification to a urine pH <7.0 is recommended and can be frequently achieved with vitamin C. Vitamin C functions as a proton donor in many biochemical reactions, providing a means for proton accumulation and overall acidification of the urine.¹

For the elimination of the calcified plaque, different protocols have been suggested based on the location, severity, and implantation into the surrounding tissue. Studies have shown that surgical exploration and pyelotomy have been effective invasive procedures for removal of encrusted material within the kidneys of transplant patients, whereas also showing a benefit in nontransplant patients.¹ Recently, percutaneous approach with encrustation debulking has shown increased success rates in the treatment of encrustations associated with staghorn calculus in transplanted kidneys.² Although shockwave lithotripsy provides a means for stone fragmentation in most situations, studies have suggested that the emitted sound waves may have a difficult time fragmenting the underlining encrustations because of their tight adhesion to the urothelial cell walls.¹

Conclusion

AEP is a unique urologic disease and proper diagnosis and management require a high index of suspicious in the at-risk patient. Common risk factors include immunosuppression, persistently alkaline urine, and chronic urinary tract infections with urease-producing bacteria, especially Corynebacterium. Treatment for AEP often involves a combined approach, including eradication of the underlying bacterial infection, acidification of the urine, and debridement of the bulky and or obstructing encrustations. With early identification and multimodal therapy, AEP can be reversed and renal function preserved.

Abbreviations Used

AEP

alkaline-encrusted pyelitis

CT

computed tomography

Disclosure Statements

No competing financial interests exist.

Funding Information

No funding was received for this article.

Cite this article as: Johnson M, Perkins SQ, Leavitt D (2020) Alkaline-encrusted pyelitis causing to renal failure in a transplant kidney: treatment with percutaneous nephrolithotomy and urinary acidification, Journal of Endourology Case Reports 6:4, 435–437, DOI: 10.1089/cren.2020.0183.