R. Kapoor

Prospective evaluation of safety and efficacy of the supracostal approach for percutaneous nephrolithotomy

Objective  To prospectively evaluate the safety and efficacy of the supracostal approach for percu‐taneous nephrolithotomy (PCNL), as it is usually avoided because of concerns about potential chest complications.

Substitution urethroplasty for anterior urethral strictures: a critical appraisal of various techniques

To retrospectively compare the outcome of various techniques of substitution urethroplasty.

Association of HLA‐G promoter and 14‐bp insertion–deletion variants with acute allograft rejection and end‐stage renal disease

The aim of this study was to investigate the HLA-G 14-bp insertion/deletion (I/D) polymorphism among end-stage renal disease (ESRD) patients. Cytomegalovirus (CMV) infection, acute allograft rejection (AR) and overall survival after renal transplantation was investigated in 300 ESRD patients and 302 age, sex and ethnicity-matched controls. Sequencing was performed to evaluate the impact of HLA-G promoter region single-nucleotide polymorphisms (SNPs) whereas semi-quantitative PCR method was used to determine the probable HLA-G expression pattern among ESRD and AR cases. Further, soluble human leukocyte antigen (HLA)-G (sHLA-G) expression levels were compared in AR vs non-AR cases in the light of HLA-G 14-bp I/D polymorphism. Increased risk was found for 14-bp D/D (deletion-DD) genotype and 14-bp D allele [DD: odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.03-2.06, P value = 0.0358; D: OR = 1.29, 95% CI = 1.03-1.62, P value = 0.0277], respectively for ESRD and CMV infection (DD: OR = 2.70, 95% CI = 1.45-5.05, P value = 0.0021; D: OR = 1.94, 95% CI = 1.22-3.08, P value = 0.0052). Nearly fourfold (OR = 3.62, 95%CI = 1.61-8.14, p = 0.0039) risk was observed for 14-bp I/I (insertion-II) genotype for AR. Survival analysis showed increased overall survival (OS) (AR or death) for 14-bp D/D genotype. HLA-G promoter region sequencing was carried out among 60 ESRD patients and 100 normal controls which showed increased risk for -964 G>A, -725 C>G/T and -486 A>C SNPs. -964 G>A and -725 C>G/T SNPs showed risk association for AR patients. High level of HLA-G transcripts was observed among non-AR patients. Further soluble HLA-G (sHLA-G) showed increased levels in ESRD patients (mean ± SEM; 62.16 ± 2.43 U/ml) as compared to controls (mean ± SEM; 21.06 ± 3.89 U/ml) (P = <0.0001). The 14-bp I/I, 14-bp I/D and 14-bp D/D genotypes showed significantly higher levels of sHLA-G among non-AR as compared to AR patients.

Acute urinary retention: defining the need and timing for pressure-flow studies.

Objective To investigate the utility of ‘late’ pressure‐flow studies in predicting the outcome of prostatectomy for acute urinary retention.

Is Laparoscopic Approach Safe for Ectopic Pelvic Kidneys

Objective: To assess the feasibility and safety of a laparoscopic approach to pelvic kidneys for ablative and reconstructive surgery. Methods: BetweenJanuary 2002 and February 2005, 6 patients with a left pelvic kidney; 2 with ureteropelvic junction obstruction, 2 with nonfunctioning kidney and 2 with pelvic stones were selected. These patients underwent dismembered pyeloplasty, simple nephrectomy and pyelolithotomy by laparoscopic approach. For pyeloplasty, omitting the prior retrograde stent facilitated dissection around the pelvis, which was identified first and then the ureter was traced downwards. Dismembered pyeloplasty was done by continuous sutures using 4–0 vicryl over a double-J stent placed antegradely. During nephrectomy, the ureter was identified over the iliac vessels and divided first. Subsequent dissection was carried out after lifting the kidney to identify ectopic renal vessels. Pyelolithotomy was performed for a large single pelvic stone after placing the ureteric catheter and confirming the stone’s position by fluoroscopy. Results: One patient with pyelolithotomy was converted to open surgery while the others were completed laparoscopically.Mean hospital stay was 4.16 (range 3–5) days, blood loss 115 (range 30–300) ml and mean operative time was 170 (range 140–220) min. There were no post-operative complications. After pyeloplasty there was significant improvement in renal function and drainage pattern on diuretic scan at 11 and 12 months. Conclusion: The laparoscopic approach provides all the benefits of a minimally invasive procedure to the patients. Due to the different locations of renal vessels, it is safe to approach the ureter first when performing nephrectomy. When performing pyeloplasty, omitting the prior stent placement helps in the identification and dissection of the renal pelvis.

HLA-G gene expression influenced at allelic level in association with end stage renal disease and acute allograft rejection.

BACKGROUND Human leukocyte antigen (HLA)-G is a non-classical major-histocompatibility complex class-I molecule associated with immunosuppressive function. We have evaluated the impact of HLA-G allele associated with untranslated-region (UTR)-haplotype in end stage renal disease (ESRD) and acute allograft rejection (AR) cases. The mRNA levels of different HLA-G isoforms were evaluated in ESRD and AR cases. Subsequently, the total HLA-G mRNA levels and protein concentration were evaluated against its UTR-haplotype among ESRD and AR cases. METHODOLOGY Sequence based typing of the promoter region was carried-out to evaluate the impact of HLA-G haplotype in 350 ESRD cases and 300 controls. HLA-G gene expression was evaluated at the transcriptional level using semi-quantitative and quantitative PCR, whereas protein concentration was determined by ELISA among both cases and control. RESULTS Increased risk was observed for G*01:01:01:03, G*01:01:02, G*01:06 and G*01:05:N haplotypes while G*01:01:01:01 and G*01:04:01 haplotypes showed a protective effect in ESRD and AR cases. Higher level of soluble HLA-G isoforms (G5 and G6) was observed among ESRD cases. Reduced levels of soluble isoform (G5) and increased levels of membrane bound (G1 and G3) isoforms were found among AR cases, revealing risk association. Decreased HLA-G expression was observed at both mRNA and protein level for G*01:01:01:03 and G*01:05:N haplotypes in ESRD and AR cases. CONCLUSIONS These results suggest that the variation in the expression profile of membrane bound and soluble isoforms may modulate the risk for ESRD and AR. UTR-haplotypes appear to be involved in different HLA-G expression patterns at transcriptional and translational levels.

POLYMORPHISMS IN THE VITAMIN D RECEPTOR AND THE ANDROGEN RECEPTOR GENE ASSOCIATED WITH THE RISK OF UROLITHIASIS

Transcriptional activity of the vitamin D receptor (VDR) gene is regulated by androgen receptor (AR) gene and both are associated with renal stone formation. We examined gene polymorphisms of VDR (PCR-RFLP) and AR (GeneScan analysis) in 125 stone formers and 150 controls from north India. Genotype Ff of Fok-I and Tt of Taq-I demonstrated significantly higher risk (P<0.001, OR=3.559 and P=0.019, 1.830 respectively). Variant f allele exhibited 1.7-folds higher risk. Ff of Fok-I and Aa of Apa-I gene polymorphism showed higher risk in males only. Mean CAG repeat was significantly higher in hypercalciuric patients as compared to normocalciuric (mean=21.62 ± 3.384 vs. 20.11 ± 3.182; P=0.034). Combined effects 1.8-folds higher risk in patients with Tt genotype of Taq-I and short CAG repeat. Thus, association of FokI and TaqI VDR gene polymorphisms suggest VDR as an important genetic marker for urolithiasis. Further, patients with combination of Tt of Taq-I and short CAG repeat were at higher risk for stone formation.

Is Fluoroscopy Essential for Retrieval of Lower Ureteric Stones

Introduction: The aim of this study was to assess the efficacy of ureteroscopy for lower ureteric stones without the use of fluoroscopy. Patients andMethods: Between June 2001 and January 2005, a total of 110 patients with a mean age of 33.5 years (range 12–65) suffering from of lower ureteral calculi (below the upper margin of the sacroiliac joint) prospectively underwent ureteroscopic removal. Retrograde pyelography was avoided, and no safety guidewire was placed. Whenever required, the ureteric meatus was dilated with a ureteric balloon under direct vision. Double-J stent placement was done with the aid of ureteroscopy. A fluoroscope was kept standby. The patients had a postoperative X-ray of the kidney-ureter-bladder region to document the stone clearance. Results: The mean stone size was 8.7 mm (range 6–15). Complete clearance without the use of fluoroscopy was achieved in 99 patients (94.2%). Fluoroscopy was required in 6 patients (4%) for calcified stricture (n = 1), duplex system (n = 1), narrow and tortuous meatus causing difficulty in passing the 5-Fr balloon dilator (n = 3), and confirmation of spontaneous passage of the stone (n = 1). Of the 13 patients who required balloon dilatation it was successfully achieved without fluoroscopy. Double-J stenting was done due to mucosal ulceration (n = 3), polypoid reaction (n = 2), and perforation (n = 1). All these patients had correct placement of the stent, as confirmed by X-ray of the kidney-ureter-bladder region postoperatively. Conclusions: To uphold the notion for radiation exposure to be as low as reasonably achievable, ureteroscopic stone retrieval can safely be done without the use of fluoroscopy in a significant number of patients.

Percutaneous Nephrolithotomy in Ectopically Located Kidneys and in Patients with Musculoskeletal Deformities

Objective: To assess the feasibility, safety and results of percutaneous nephrolithotomy (PNL) in ectopically located kidneys and in patients with musculoskeletal deformities. Patients and Methods: Thirteen such patients underwent PNL between June 2005 and May 2008. Mean stone size was 27.4 mm (16–37 mm). Six patients had severe kyphoscoliosis, 2 patients each had achondroplasia, cross-fused ectopia and pelvic ectopic kidney, and 1 patient had thoracic kidney. All had a preoperative CT scan of the abdomen. Preoperative ultrasound- or CT-guided percutaneous nephrostomy (PCN) was done in 10 patients. Three patients underwent laparoscopic-assisted PNL. All underwent standard PNL. The stone-free rate, complication rate and need for secondary intervention were evaluated. Results: PNL was successfully completed in all. A second ultrasound-guided intraoperative puncture was required in 2 patients. Re-look PNL was required in 1 patient and the same patient later required shock wave lithotripsy for complete stone clearance. The remaining 12 patients (92.3%) were rendered stone-free in a single sitting. Conclusion: PNL is a feasible and effective modality in anomalous kidneys. Preoperative planning with CT and image-guided PCN is helpful in these situations. Laparoscopic-assisted PNL can be safely performed in patients where access to a renal collecting system by fluoroscopy or image-guided assistance (ultrasound or CT scan) is not possible.

Impact of chemokine receptor CCR2 and CCR5 gene polymorphism on allograft outcome in North Indian renal transplant recipients.

The CC chemokine receptors, CCR2 and CCR5, contribute to the trafficking of leucocytes into the sites of the immune response in transplanted kidney. Therefore, the inter‐individual differences in CCR2 and CCR5 gene expression, due to single‐nucleotide polymorphism, have the potential to influence various immune responses within the graft, eventually deciding the allograft outcome. In this study, we genotyped 296 North Indian renal transplant recipients and 277 healthy controls for CCR2V64I and CCR5‐Δ32 polymorphisms by sequence‐specific primers and restriction fragment length polymorphism and examined their association with allograft outcome. The frequency of CCR2+/64I (heterozygous) and CCR2‐64I/64I (homozygous mutant) genotype were comparatively higher in non‐rejecters when compared with transplant recipients experiencing one or more than one rejection episode (20.4% versus 8.2%), thereby resulting in a significantly reduced risk of allograft rejection (OR = 0.331, P = 0.026). The Kaplan–Meier curve also suggested higher mean time for the first rejection episode in CCR2‐64I allele carriers (32.83 ± 1.36 months) when compared with CCR2+/+ recipients (28.09 ± 0.93 months, log P = 0.027). The CCR5‐Δ32 variant had no profound effect on allograft outcome. In conclusion, our study confirmed CCR2‐64I allele to be associated with reduced risk for allograft rejection in North Indian transplant recipients influencing allograft outcome.