How Does Acute Urolithiasis Present After Renal Denervation?

Introduction

P ain afflicts 60% of patients with autosomal dominant polycystic kidney disease (ADPKD). ¹ Chronic pain in patients with ADPKD is postulated to arise from combinations of mechanical back pain because of spinal degeneration and cyst enlargement resulting in compression of surrounding tissues, traction on the renal pedicle, and distention of the renal capsule. We have implemented a technique of laparoscopic renal denervation for intractable pain in this pediatric population and have also extended it to the Fraley syndrome, loin pain hematuria syndrome, and one patient with chronic pain after multiple open renal procedures.

We have 17 children with a total of 26 renal units in this group that underwent renal denervation. This is the same cohort from a 2008 a study on renal denervation by Casale and associates. ² All the patients in this cohort remain pain free with an average of 47 months of follow up.

The overall incidence of pediatric urolithiasis ranges from 0.1% to 5%, and reported prevalences account for 1 in 1000 to 1 in 7600 hospitalizations in the United States. ³ Urolithiasis has developed in the patients in our cohort. A question frequently asked by both patients and parents is, “What happens if kidney stones develop?” We hypothesize that these patients do not present with flank pain, but present with a more generalized abdominal complaint. We present our experience with the presentation of stones in this specific population.

Patients and Methods

Five patients aged 8 to 16 years (mean age 11.4 years) with a history of laparoscopic renal denervation presented with acute abdominal symptoms and received a diagnosis of obstructing urolithiasis. This is a retrospective review of a prospective database with Institutional Review Board approval. Data collected included acute presentation, radiologic imaging to diagnose, side of presentation, type of stone, surgical intervention if needed, and recurrence rates. Patients were followed by ultrasonography 3 months after the procedure or stone passage as well as with a 24-hour urine analysis.

Results

Five patients underwent seven laparoscopic renal denervation procedures for right flank pain (1), left flank pain (2), and bilateral (2) flank pain. Of the five patients, three had a history of four episodes of nephrolithiasis that was treated conservatively in three episodes and with ureteroscopy in one. There were a total of 12 episodes of acute urolithiasis in this cohort after renal denervation.

The patient who underwent a right renal denervation for ADPKD presented with three acute episodes of urolithiasis: One in the denervated right kidney and two in the left kidney that was not denervated. These stones were diagnosed by ultrasonography delineating an obstructing proximal stone with hydronephrosis. The pain from the right stone was periumbilical and epigastric with nausea and two episodes of vomiting after gross hematuria. The right stone measured 4 mm. This same patient had two other episodes of urolithiasis but on the contralateral nondenervated left kidney. With these two episodes, the patient had typical flank pain, nausea, as well as gross and microscopic hematuria as symptoms before diagnosis of obstructing urolithiasis. These left stones measured 3 and 4 mm.

Two patients underwent left renal denervations; one for Fraley syndrome and the other because of chronic pain after multiple open renal operations. Both of these patients had an acute stone episode in the denervated kidney. One of these two patients, the one with the multiple open procedures, had an episode in the contralateral nondenervated kidney. In the two episodes in the denervated kidneys, one patient presented with periumbilical and epigastric discomfort, nausea, gross hematuria in one patient, and both patients presented with microscopic hematuria. Neither of these patients presented with vomiting with any episode. One of these stones measured 5 mm, was located at the ureterovesical junction, and was diagnosed by ultrasonography. The other stone was 9 mm at the uretropelvic junction (UPJ) and was diagnosed by CT scan. Both had hydronephrosis on their respective study. The patient with the nondenervated kidney presented with right flank pain, nausea, anorexia, and gross hematuria. This right stone measured 6 mm at the UPJ with hydronephrosis by ultrasonography.

The last two patients had bilateral asynchronous renal denervations. In one patient, two stones developed on the right and one on the left. In the other patient, two stones developed on the left and one on the right. Interestingly, all of these episodes were accompanied by periumbilical and epigastric pain, nausea, vomiting, as well as gross and microscopic hematuria. The stones in the right-sided episodes were proximal in two (6 and 7 mm) and distal in one (6 mm), all diagnosed by CT scan. The stones in the left-sided episodes were proximal in all three and were diagnosed by ultrasound in two (7 mm and 5 mm) and CT scan (4 mm) in one. All the studies revealed hydronephrosis.

Of the five patients and total of 12 episodes, concomitant infection did not develop in any patient. Of the 12 stone episodes, 9 (75%) had surgical intervention with ureteroscopy and stent placement. These stones were all 5 mm or more in their largest measurement. In the remaining three (25%) episodes, the stones were passed with conservative management. These three stones were 5 mm or less. All 12 stones were a mixture of calcium monohydrate and dihydrate.

The most common abnormal 24-hour urine analysis parameter was a low volume in four of the five patients with a high urinary sodium and low citrate. These patients are all undergoing periodic evaluation with 24-hour urine analysis after their abnormal parameters stabilized. The recurrence rate was 4/12 (33%) episodes during the stabilization period of the urinary parameters. One patient had hypercalciuria and hypercalcemia because of an elevated parathyroid hormone. This patient underwent treatment with resolution of hypercalcemia and hypercalciuria. This patient has been stone free since then. To date, the remaining patients also remain stone free.

Discussion

We have also seen, as others have noted in the literature, a dramatic rise in the overall incidence of pediatric urolithiasis. ¹ We present an unusual cohort of patients who underwent renal denervation procedures for intractable pain. Although our success rate for resolution of pain has been quite promising in this population, the success rates in the literature vary, with the worse outcome being 25% success long term. ² Recurrence of pain in most patients who undergo renal denervation may be from nerve regeneration, which has been demonstrated 28 days postrenal transplantation in human allografts and isografts.

Nephrolithiasis in the transplant kidney is a relatively uncommon event. In our experience, these patients present with diffuse abdominal pain with nausea and anorexia as well as hematuria. Our renal denervated population is not spared from urolithiasis. One question asked by families and patients is, “Will I be able to feel a kidney stone after the denervation?” At first, we were unsure of this phenomenon. It appears that we can now answer, “Yes, but it will be different.”

It is interesting that in all of our patients, periumbillical and epigastric discomfort developed with stone presentation on their denervated side. They all had nausea with or without vomiting. They all had microscopic hematuria, and 80% had gross hematuria. Furthermore, when these patients had stones in their nondenervated kidney, the symptoms were those of typical stone passage with ipsilateral flank pain, nausea, and hematuria.

We are unsure why pain in the periumbilical and epigastric area developed with a retroperitoneal structure in these patients. It is understood that abdominal pain is divided into visceral and parietal components. Parietal pain is sharp, easily localized, and based on peritoneal inflammation. Visceral pain is vague and poorly localized based on the structure's origin as a foregut (epigastric pain), midgut (periumbilical pain), or hindgut (hypogastrium pain) structure. ⁴ It is possible that the obstructed kidney stimulated nearby nerve structures that are responsible for foregut and midgut visceral pain sensation. This would account for the epigastric discomfort and vomiting.

It should be noted that all of these patients presented with hydronephrosis and that ureteral distention could be responsible for these patients' symptoms. We do see periumbilical pain with acute appendicitis, so it is possible that ureteral inflammation or distention from obstruction can produce the same pain because the two problems can have the same presentation when the stone is right sided. Nonetheless, it would not explain why the left side presentation would be this way after renal denervation.

Conclusions

Stone-related pain in patients undergoing laparoscopic renal denervation and nephropexy is not a typical presentation. One needs to be wary of vague abdominal pain in this population and include nephrolithiasis in the differential diagnosis, particularly with the presence of micro- or macroscopic hematuria; a renal ultrasonographic screening may uncover nephrolithiasis in this setting.