ABSTRACT: To address the molecular mechanisms that the vitamin D receptor (VDR) in the kidney might contribute to decreased renal calcium reabsorption in idiopathic hypercalciuria using genetic hypercalciuric stone-forming (GHS) rats.
We silenced the VDR gene in the GHS and normal control (NC) rat kidney in vivo using adenovirus vector-delivered microRNA targeting VDR through renal venous transduction. On days 3-21 after injection with adenovirus, the expression levels of the VDR, calcium-sensing receptor, and epithelial calcium transporters in the kidney were detected. The urine calcium and serum calcium, phosphorus, 1,25(OH)(2)D(3), and parathyroid hormone levels were measured.
The basal expression levels in the kidney tissues of VDR, calbindin-D(28k), and calcium-sensing receptor were significantly greater in the GHS rats than in the NC rats, and the basal expression levels of transient receptor potential vanilloid receptor subtype 5, transient receptor potential vanilloid receptor subtype 6, calbindin-D(9k), and plasma membrane calcium-adenosine triphosphatase were significantly lower in the GHS rats than in the NC rats. VDR knockdown in the kidney caused significant increase in renal transient receptor potential vanilloid receptor subtype 5, sodium/calcium exchanger, and calbindin-D(9k) expression levels in the GHS rats. The GHS rats excreted significantly more urine calcium after VDR knockdown. The serum calcium, phosphorus, parathyroid hormone, and 1,25(OH)(2)D(3) levels were not altered during the study period in the GHS and NC rats.
Our findings suggest that VDR knockdown in the kidney can upregulate the expression of transient receptor potential vanilloid receptor subtype 5 in GHS rats. However, VDR depletion results in an increase in urine calcium excretion. The role of VDR in the hypercalciuric formation needs to be elucidated further.
Urology 12/2011; 78(6):1442.e1-7. · 2.43 Impact Factor
ABSTRACT: To report the incidence, risk factors, and outcomes of subcapsular renal haematoma (SRH) after ureteroscopic lithotripsy (URSL) using holmium:yttrium-aluminum-garnet (Ho:YAG) laser to treat ureteric stones.
Prospective data from 2848 URSLs performed between January 2003 and September 2010 were retrospectively analysed. In all 11 patients were identified as having a SRH after URSL if they had persistent severe ipsilateral flank pain or a palpable mass within a day of surgery, or presented with radiographic evidence of a SRH. Risk factors for the development and course of the SRH were reported.
Of the 2848 consecutive patients treated with URSL using Ho:YAG laser, 11 (0.4%) developed a SRH after surgery. Patients who developed a SRH had larger stones (1.4 vs 0.9 cm, P < 0.001), more severe ipsilateral hydronephrosis (P < 0.001), longer operation duration (41 vs 33 min, P < 0.001), and higher perfusion pressure of hydraulic irrigation (176.8 vs 170.2 mmHg, P < 0.001) than patients who did not develop a SRH. Patient age, sex, body mass index, presence of diabetes mellitus, history of urolithiasis and hypertension, presence of multiple stones, stone location and flow rate of hydraulic irrigation were not statistically different in patients who did or did not develop a SRH. Most patients were managed conservatively, with no further intervention or with a flank drain, until the SRH resolved. Overall, in three patients the SRH resolved with no further intervention, six patients were treated with a drain only, and two patients had open surgery within a day of presenting with SRH.
The rate of development of SRH after URSL is very low. Most patients who present with a SRH after URSL, can be treated conservatively with no intervention or with a drain only.
BJU International 08/2011; 109(8):1230-4. · 2.84 Impact Factor
ABSTRACT: What’s known on the subject? and What does the study add? Experimental data have shown that VDR overexpression in the duodenum and kidney cortex is a biological characteristic of genetic hypercalciuric stone-forming rats (GHS rat), and a link between idiopathic calcium stone formation and the microstatellite marker D12S339 (near the VDR locus) has been proven in humans. Our study shows that VDR can positively regulate the mRNA and protein expression of TRPV5, calbindin-D28k and PMCA1b in NRK cell lines. VDR knockdown results in a decrease in intracellular Ca²⁺ concentration in NRK cell lines. The effect of the elevated VDR level in the kidney on hypercalciuria and the underlying mechanisms need to be further addressed.
• To determine the effects of vitamin D receptor (VDR) on hypercalciuria and the mechanisms underlying such effects.
• The adenovirus vector-delivered microRNA targeting rat VDR was constructed. We infected the normal rat kidney epithelial cell line NRK (Cellbank, China) with the adenovirus and then collected the cells at 0, 48, 72, 96, 120 h after infection. The mRNA and protein levels of VDR and VDR-dependent epithelial Ca2+ transport proteins were detected using real-time polymerase chain reaction and Western blot assays, respectively. • Fluorescent Ca²⁺ indicator Fluo-4 NW (Fluo-4 NW calcium assay kit, Molecular Probes, Invitrogen, USA) and laser scanning confocal microscope (Olympus, FV500-IX71, Japan) were used to detect the cytosolic free Ca²⁺ concentration at different time points after infection.
• The mRNA and protein level of VDR, transient receptor potential vanilloid receptor subtype 5 (TRPV5), calbindin-D28k and plasma membrane Ca²⁺-ATPase (PMCA1b) in infected NRK cells was significantly lower at 72 and 96 h after infection than that in control cells. • There was no significant difference between the two groups in the mRNA and protein level of TRPV6 and the Na⁺/Ca²⁺-exchanger (NCX1). • Furthermore, VDR knockdown results in a decrease in intracellular Ca²⁺ concentration ([Ca²⁺]i) in NRK cell lines.
• Our study shows that VDR can positively regulate the mRNA and protein expression of TRPV5, calbindin-D28k and PMCA1b, but not of TRPV6 or NCX1, in NRK cell lines. VDR knockdown results in a decrease in [Ca²⁺]i in NRK cell lines. • The effect of the elevated VDR level in the kidney on hypercalciuria and the mechanisms underlying need to be further addressed.
BJU International 04/2011; 107(8):1314-9. · 2.84 Impact Factor
ABSTRACT: We compared the efficacy and safety of percutaneous nephrolithotomy (PCNL) with different intracorporeal lithotriptors for proximal ureteral stones in patients with severe hydronephrosis.
We retrospectively analyzed the records of 192 patients with proximal ureteral calculi and severe hydronephrosis who underwent PCNL between February 2003 and December 2007. Calculi were fragmented with a pneumatic lithotriptor in 44 patients (group 1), Swiss Lithoclast Master in 54 (group 2), low-power holmium:yttrium-aluminum-garnet (YAG) laser in 56 (group 3) and high-power holmium:YAG laser in 38 (group 4). Patients were assessed about 12 months postoperatively with intravenous urography and ultrasonography for late complications. Stone size, operative time, stone-free rate, and follow-up were analyzed in each group.
Mean stone size for different groups were 16.2 +/- 2.8 mm, 16.6 +/- 2.1 mm, 16.0 +/- 2.7 mm, and 16.4 +/- 1.1 mm, respectively. Average operative time for different groups were 118 +/- 17 minutes, 81 +/- 10 minutes, 85 +/- 14 minutes, 110 +/- 16 minutes, respectively. Group 2 and group 3 showed superior outcomes of shorter operative time (P = 0.000). The overall stone-free rate was 86.5%. As stratified by lithotriptors, the stone-free rate was 81.8% in group 1, 92.9% in group 2, 88.9% in group 3, and 78.9% in group 4 (P = 0.190). No significant difference was found among the groups in terms of blood loss and postoperative hospital stay. Repeated PCNL or shockwave lithotripsy was necessary as an auxiliary procedure in 26 patients. The overall complication rate was 18.2%; most complications were minor and insignificant. During the follow-up, ureteral stricture developed in 10 patients and new renal stones developed in 4 patients.
PCNL combined with Swiss Lithoclast Master or low-power holmium:YAG laser is the preferred endourologic modality for the management of proximal ureteral calculi in patients with severe hydronephrosis.
Journal of endourology / Endourological Society 02/2010; 24(2):201-5. · 1.75 Impact Factor