Kelley-Seegmiller Syndrome: Urolithiasis, Renal Uric Acid Deposits, and Gout: What is the Role of the Urologist?

Kelley-Seegmiller syndrome (KSS) is a disorder that occurs when there is a partial deficiency of the enzyme hypoxanthine guanine phosphoribosyl transferase. It is involved in the metabolism of purines, clinically manifesting as hyperuricemia, hyperuricosuria, gout arthritis, and urolithiasis. The aim of this article is to present the case of a 33-year-old male with KSS, with left ureteral colic, and a 5-mm, 323-HU ureteral calculi, successfully managed with conservative management. It is critical to recognize that most urologists are not familiar with this inborn metabolic error and 75% of these patients will be affected by urolithiasis, thus making it a very critical and significant disease in our practice.

The ability of a limited metabolic assessment to identify pediatric stone formers with metabolic abnormalities.

INTRODUCTION: American Urological Association guidelines recommend a urinary metabolic evaluation after the first stone event in all pediatric stone patients. Prior studies identified hypercalciuria and urine hypovolemia as the most common abnormalities in children with urolithiasis. Recent data suggest that hypocitraturia is most prevalent. It was hypothesized that a limited evaluation would detect the majority of clinically significant metabolic abnormalities in pediatric stone formers. MATERIAL AND METHODS: A retrospective analysis of all children (<18 years of age) with renal/ureteral calculi evaluated at the study institution from 2005 to 2015 was performed. Children with ≥ one 24-h urinary metabolic profile after a clinical visit for renal/ureteral calculi were included. Those with bladder stones and those with undercollection or overcollection or missing urinary creatinine were excluded. Demographics and data from the first urinary metabolic profile and stone analyses were collected. The sensitivity, specificity, and positive and negative predictive value (NPV) of a limited urinary metabolic evaluation consisting of four parameters (24-h calcium, citrate, and oxalate and low urinary volume) were compared to a complete urinary metabolic profile. The number and type of metabolic abnormalities that would have been missed with this limited evaluation weredetermined. RESULTS: Of 410 patients, 21 were excluded for age ≥18 years, 13 for bladder stones, 248 for overcollections, 38 for undercollections, and 10 for missing creatinine. This left 80 patients for inclusion: median age 11.4 years, 60% female, and 96.3% white. Of the entire cohort, 69.6% had hypocitraturia, 52.5% had low urine volume, and 22.5% had hypercalciuria. Sensitivity was 87.5%. Specificity could not be calculated because no patients had a normal complete metabolic evaluation. The NPV was zero, and the positive predictive value was 100%, but these are artifacts resulting from the absence of patients with a normal complete metabolic evaluation. Of the 80 patients, 10 had at least one abnormality missed by a limited metabolic evaluation (Table 1). The missed abnormalities were high pH (n = 6), abnormal 24-h phosphorus (low in 1 patient and high in 1 patient), low 24-h magnesium (n = 3), low 24-h potassium (n = 3), and high 24-h sodium (n = 4). DISCUSSION: A limited urinary metabolic evaluation would have detected the vast majority of clinically significant metabolic abnormalities in the study sample. Approximately two-thirds of the study patients submitted inadequate 24-h urine specimens. CONCLUSIONS: A simplified approach to metabolic evaluation in first-time stone formers with a stone analysis available was proposed. This streamlined approach could simplify the metabolic evaluation and reduce health care costs.

Ureteral access sheath use and stenting in ureteroscopy: effect on unplanned emergency room visits and cost.

PURPOSE: We studied the impact of stented and unstented ureteroscopy on unplanned emergency room (ER) return visits, medical costs, and whether use of a ureteral access sheath precluded uncomplicated ureteroscopy. PATIENT AND METHODS: A series of 161 consecutive patients undergoing ureteroscopy for renal or ureteral stones was evaluated retrospectively. We examined sex, age, stone size, stone location, use of a ureteral access sheath, use of a ureteral stent, unplanned ER visits, unplanned imaging, and interventions. Medical costs were calculated according to British Columbia Medical Services Plan rates. RESULTS: In the 107 stented and 54 unstented patients, the mean stone sizes were 9 and 7 mm, respectively (P = 0.01), and ureteral access sheaths were used in 55% and 35% (P = 0.002). Stent use did not differ by patient age or sex or stone location. The ER return rates were 17% v 22% for the stented and unstented patients, respectively (P = 0.40), with emergency CT scans being performed in 28% v 75% of the returning patients (P = 0.02), hospital readmission in 22% v 58% (P = 0.05), and urgent decompression in 0 v 25% (P = 0.04). Among patients who were not stented, 37% of those treated using ureteral access sheaths v 14% treated without access sheaths returned to the ER (P = 0.04). The median costs were CDN dollars 1212 for stented and CDN dollars1071 for unstented patients (P < 0.0001). CONCLUSIONS: The unplanned ER return rate is similar whether patients are stented or unstented after ureteroscopy. The median cost saving for unstented patients is approximately CDN dollars140. Use of a ureteral access sheath precludes uncomplicated ureteroscopy, and a ureteral stent should be placed in these cases.

Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis: role of mast cells.

The effects of ultramicronized palmitoylethanolamide were evaluated on pain behaviours and markers of mast cell (MC) activity in a rat model of endometriosis plus ureteral calculosis (ENDO+STONE)-induced viscerovisceral hyperalgesia (VVH). Female Sprague-Dawley rats that underwent surgical induction of endometriosis were randomly assigned to receive active (ultramicronized palmitoylethanolamide 10 mg·kg(-1)·d(-1), orally) or placebo treatment for 25 days. At day 21, they underwent ureteral stone formation and were video-recorded till day 25 to evaluate ureteral and uterine pain behaviours. At autopsy (day 25), ureteral condition and number and diameter of endometrial cysts were evaluated. The following were then measured: number and percentage of degranulating MCs, number of vessels, chymase, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and Flk-1 (VEGF receptor) in cysts, and NGF in dorsal root ganglia (DRG). Ultramicronized palmitoylethanolamide-treated vs placebo-treated rats showed significantly lower number, duration and complexity of ureteral crises, shorter duration of uterine pain, and smaller cyst diameter (0.0001 < P < 0.004); a significantly higher percentage of expelled stones (P < 0.0001); significantly lower MC number (P < 0.01), vessel number (P < 0.01), chymase (P < 0.05), NGF (P < 0.05), VEGF (P < 0.01), and Flk-1 (P < 0.01) expression in cysts and NGF expression in DRG (P < 0.01). In all animals, the global duration of ureteral crises correlated linearly and directly with cyst diameter, MC number and chymase in cysts, and NGF in cysts and DRG (0.02 < P < 0.0002). Ultramicronized palmitoylethanolamide significantly reduces VVH from ENDO+STONE, probably by modulating MC expression/activity in cysts, thus reducing central sensitization due to noxious signals from endometriotic lesions. The results suggest potential utility of the compound for VVH in clinics.

Effects of PDE5 Inhibitors and sGC Stimulators in a Rat Model of Artificial Ureteral Calculosis.

Urinary colics from calculosis are frequent and intense forms of pain whose current pharmacological treatment remains unsatisfactory. New and more effective drugs are needed to control symptoms and improve stone expulsion. Recent evidence suggested that the Nitric Oxide (NO) / cyclic guanosine monophosphate (cGMP)/phosphodiesterase type 5 (PDE5) system may contribute to ureteral motility influencing stone expulsion. We investigated if PDE5 inhibitors and sGC stimulators influence ureteral contractility, pain behaviour and stone expulsion in a rat model of ureteral calculosis. We investigated: a) the sex-specific PDE5 distribution in the rat ureter; b) the functional in vitro effects of vardenafil and sildenafil (PDE5 inhibitors) and BAY41-2272 (sGC stimulator) on induced ureteral contractility in rats and c) the in vivo effectiveness of vardenafil and BAY41-2272, alone and combined with ketoprofen, vs hyoscine-N-butylbromide alone or combined with ketoprofen, on behavioural pain indicators and stone expulsion in rats with artificial calculosis in one ureter. PDE5 was abundantly expressed in male and female rats' ureter. In vitro, both vardenafil and BAY41-2272 significantly relaxed pre-contracted ureteral strips. In vivo, all compounds significantly reduced number and global duration of "ureteral crises" and post-stone lumbar muscle hyperalgesia in calculosis rats. The highest level of reduction of the pain behaviour was observed with BAY41-2272 among all spasmolytics administered alone, and with the combination of ketoprofen with BAY41-2272. The percentage of stone expulsion was maximal in the ketoprofen+BAY41-2272 group. The NO/cGMP/PDE5 pathway is involved in the regulation of ureteral contractility and pain behaviour in urinary calculosis. PDE5 inhibitors and sGC stimulators could become a potent new option for treatment of urinary colic pain.

New location of milk-of-calcium.

A case of milk-of-calcium with an exceptional location is reported. The characteristics of milk-of-calcium are presented, with stasis and urinary tract infection being the most important etiologic factors in this case. Structurally the stones are formed by a central core of calcium phosphate surrounded by magnesium-ammonium phosphate (struvite).

Damage attributable to extracorporeal shockwave lithotripsy and deposition of calcium oxalate crystals on ureteral stents.

Ureteral stents have been widely used during and after SWL depending on the size of the stones and the condition of the urinary tracts. The use of stents can help to reduce complications and contributes to stone passage. However, some reports note complications that were attributed to indwelling ureteral stents. We attended to the role of obstruction of ureteral stents in those complications. The aim of this study was to analyze factors that influence ureteral stent obstruction and damage caused by SWL. Crystal deposition and the damage by SWL were examined in all ureteral stents by the use of continuous flow system and were evaluated by scanning electron microscopy. The degree of crystal deposition and damage differed depending on the individual stent. The material properties of the stent surface are the major factor influencing crystal deposition and the degree of damage by SWL. The indications for ureteral stenting must be considered in each case, because the routine use of ureteral stents has a possibility to increase complications.

Early detection of infected ureteral obstruction after SWL employing C-reactive protein.

Infection of the obstructed upper urinary tract is a severe complication of stone disease. Early detection and therapy is crucial to prevent septicemia. The authors investigated prospectively whether C-reactive protein (CRP) might act as a marker for the early detection of infected upper urinary tract obstruction. The serum concentration of CRP was compared with the classic markers of inflammation--white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and temperature--in the follow-up of 85 patients undergoing 173 extracorporeal shockwave lithotripsy (SWL) treatments. Post-SWL, 69% of the patients showed dilation of the upper tract on ultrasonography and 16.5% became symptomatic and required intervention. In this group, the mean CRP value was increased 18-fold, whereas the WBC count, ESR, and temperature were not markedly raised. In contrast, patients with no need for additional treatment showed no more than a 2-fold increase in CRP. C-Reactive protein seems to be a useful indicator for the early detection of infected upper urinary tract obstruction.

[Extracorporeal shock wave lithotripsy for ureteral stones and cystine stones].

We report our experience with extracorporeal shock wave lithotripsy (ESWL) in the treatment of ureteral and cystine stones, which are known to be difficult to treat by this method. First, in order to determine the effectiveness of the ureteral catheter in the destruction of ureteral stones, we compared the clinical results of 121 patients treated without the catheter and 141 patients inserted with the catheter. There was no significant difference in the success rate between the two groups regardless of stone size, which indicates that the use of the ureteral catheter had no effect on the outcome of treatment. We then studied the clinical results of impacted ureteral stones which are especially difficult to destroy. Excretory urography was performed to non-invasively diagnose these stones, and those without visualization in the ureter below the stone were diagnosed as impacted stones and treated by ESWL without the ureteral catheter. Among the stones with a diameter of 1 to 2 cm, the success rate was significantly lower in impacted stones compared to non-impacted stone. These findings suggest that ESWL treatment without the ureteral catheter may be effective for ureteral stones with a diameter of less than 1 cm and non-impacted stones with a diameter of 1 to 2 cm, while combination therapy with other methods such as TUL may be better for other stones. We also performed ESWL on 6 patients with renal stones and 2 patients with ureteral stones which were cystine stones. Renal stones required an average 4.1 treatment with an average of 1,875 shocks per treatment, and ureteral stones required 1.5 treatment with an average of 1,833 shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical study concerning of latamoxef concentration in the obstructed urinary tract].

Urinary LMOX concentration was studied in 18 patients with unilateral ureteral obstruction. The concentration of LMOX in the urine from the mild obstructed kidney was 124 to 2,140 micrograms/ml and 10 micrograms/ml in the severely obstructed ones. The difference was probably due to the intensity and the duration of the obstruction. The patient with 99mTc-DMSA renal uptake of less than 3% also had a urinary LMOX concentration of less than 7 micrograms/ml. The above results seem to show that 7 micrograms/ml in urinary LMOX concentration is a significant figure for treatment of UTI. 99mTc-DMSA renal uptake and renal echogram were used to estimate the excretion rate of antibiotics into the urine.

[Experimental and clinical studies on calcium urolithiasis: (I) Animal model for calcium oxalate urolithiasis using ethylene glycol and 1-alpha (OH) D3].

As calcium oxalate stones are the most important component in urolithiasis, an experimental model has to be designed to clarify the pathogenesis and aid in their prevention. Hyperoxaluria as well as hypercalciuria were produced in rats by administering ethylene glycol (0.5%, in drinking water administered ad libitum) and 1-alpha (OH) D3 (0.5 micrograms/rat given every other day), respectively, for three to four weeks. Neither drug alone produced stones efficiently as did the combination regimen of these two compounds. The occurrence of stones was 77.3%, and with only a moderate degree of renal functional impairment. Biochemical and histological data were obtained using this model.

[Using prostaglandin inhibitor dicloberl in patients with ureteral calculi]. / Primenenie ingibitora prostaglandinov dikloberla u bol'nykh s kamniami v mochetochnike.

75 patients have been given prostaglandin inhibitor dicloberl in a complex therapy. Comparative analysis of traditionally treated patients with renal stones and with dicloberl in a complex therapy is presented in the article. The combination of dicloberl with tramadol was found to be more effective drug treatment for patients with renal colic. This treatment has to be applied for patients with renal stones up to 6 mm. It is an effective pharmacotherapy for excreting renal stones.

[Study of the elctrolyte level of blood, kidney tissue and concretions in nephroureterolithiasis in children]. / Ob izuchenii élektrolitnogo sostava krovi tkani pochek i konkrementov pri nefroureterolitiaze u detei

The work is based on exploration of 128 patients, aged from 3 to 14 years with different localization of renal and ureteral stones and 20 healthy children. Different variants of electrolytic disorders are described, and an attempt is made to account for them.

Erythrocyte oxidative stress in patients with calcium oxalate stones correlates with stone size and renal tubular damage.

OBJECTIVE: To investigate how erythrocyte oxidative stress relates to renal tubular damage and calcium oxalate stone size in patients as oxidative stress has been demonstrated to be associated with stone formation in disease progression. METHODS: The study included 29 controls, 29 patients with kidney stones, and 28 patients with ureteral stones. Venous blood samples were collected to measure the expression and activity of antioxidant enzymes in the isolated erythrocytes. A 24-hour urine sample was collected to measure urinary chemistry. The cellular levels of oxalate and the oxidative stress marker malondialdehyde (MDA) were determined to examine their correlations with stone size and renal tubule damage. RESULTS: Calcium oxalate stone deposition and high free radical levels in venous blood associated with high levels of urinary oxalate, glutathione S-transferases tubular damage markers, and MDA and low urinary citrate levels. Compared with the erythrocytes of controls, the erythrocytes of stone groups had significantly lower levels and activities of antioxidant proteins, namely, reduced glutathione, catalase, and copper- or zinc-superoxide dismutase. The ureteral stone group also had significantly lower erythrocyte glutathione peroxidase levels and glutathione reductase activity than the controls. Erythrocyte oxalate levels correlated positively with erythrocyte MDA levels and negatively with erythrocyte antioxidant protein activities. Erythrocyte oxidative stress, as indicated by cellular MDA levels, also correlated well with urinary glutathione S-transferases and stone size. CONCLUSION: These results suggest that oxalate-mediated oxidative stress in erythrocytes might contribute to the tubular damage and stone accumulation in patients with hyperoxaluria.