Is enalapril adequate for the prevention of renal tissue damage caused by unilateral ureteral obstruction and/or hyperoxaluria?

Unilateral ureteral obstruction (UUO) and hyperoxaluria (HOX) can lead to end-stage renal disease with tubulointerstitial fibrosis. We investigated the effects of enalapril (E), an ACE-inhibitor, on rat kidneys with either UUO or HOX. Sham-operated, UUO, HOX, UUO+HOX, UUO+E and HOX+E rats were killed 14 days after UUO and/or HOX was initiated. Rat kidney sections were histologically scored for tissue damage and monocyte/macrophage infiltration was demonstrated with ED1 antibody and measured by computer image analysis software. Serious glomerular and tubulointerstitial damage was found for UUO and HOX, consisting of glomerular basement membrane thickening, tubular dilatation/collapse, tubular basement membrane thickening and the infiltration of mononuclear leucocytes (mainly macrophages). For HOX, calcium oxalate crystals were visible. Neither the scored histological parameters nor monocyte/macrophage infiltration was significantly decreased when E-treated were compared with untreated groups. We conclude that E did not ameliorate the parameters scored in either UUO or HOX. This being contrary to findings by other research groups, we hypothesize that E may be effective only in short-term UUO/HOX, with transforming growth factor, TGF-beta1, formation becoming partly independent of Ang II in late-stage UUO/HOX, or other fibrogenic cytokines than TGF-beta1 becoming predominant.

Free and total prostate-specific antigen levels in saliva and the comparison with serum levels in men.

OBJECTIVE: We investigated free and total prostate-specific antigen (PSA) levels and free/total (f/t) ratio in the fasting saliva and compared them with the serum levels in normal individuals, in patients with benign prostatic hyperplasia (BPH) and prostate cancer. Our aim was to determine free and total PSA and f/t ratio in saliva and to improve and simplify the differentiation between BPH and prostate cancer by using saliva as an alternative to serum. METHODS: Serum and fasting saliva concentrations of free and total PSA were measured in 35 men with BPH, 16 men with stage D prostate cancer, and 25 healthy men. Serum and fasting saliva samples were collected at the same time and were analyzed on the same day at our laboratory with microparticle enzyme immunoassay technology. RESULTS: For the total of 76 men, there was a significant correlation between free and total PSA levels in each sample (r = 0.97 for serum and r = 0.44 for saliva, p<0.001). Although there was a significant difference between three groups for serum-free and total PSA levels and serum f/t ratios, no significant difference was determined between groups for salivary free and total PSA levels and salivary f/t ratios. No correlations were found between patient age and salivary PSA levels. CONCLUSIONS: Fasting salivary free and total PSA levels are not effected by high serum levels of prostatic origin. Although there was a significant difference between mean serum and salivary levels of free and total PSA in each group, the f/t ratio of saliva was very close to the serum ratio of normal subjects. Determination of free and total PSA in saliva to improve and simplify the differentiation between prostate cancer and BPH is not suitable for use as alternative measurement of serum.

Renal tubular apoptosis after complete ureteral obstruction in the presence of hyperoxaluria.

Hyperoxaluria is a well-known cause of renal stone disease and in vitro studies have shown that oxalate crystals have a stimulatory effect on apoptosis of renal tubular epithelial cells. Total and partial ureteral obstruction also have an accelerating effect on apoptosis of renal tubular epithelial cells. The aim of the present study was to investigate the apoptotic effect of unilateral ureteral obstruction in the presence of hyperoxaluria on the rat kidney. Twenty-eight male Wistar rats were divided into four groups, with seven rats in each. The groups were named G1 (control), G2 (hyperoxaluric), G3 (obstructive) and G4 (hyperoxaluric + obstructive). G2 and G4 rats were given 1% ethylene glycol (a precursor for oxalates) in their drinking water. G1 and G2 rats underwent sham operation, while left proximal ureteral ligation with a 5-zero silk suture was performed on G3 and G4 animals. The rats were sacrificed 2 weeks after the operation; left nephrectomy was then performed. We searched for the apoptotic cells by direct immuno-peroxidase detection of digoxigenin-labeled genomic DNA. The mean +/- SD values of the apoptotic cell count was 0.86+/-0.90 in G1 and 4.33+/-3.81 in G2. The values for G3 and G4 were 30.17+/-16.85 and 302.67+/-184.45, respectively. We found a statistically significant difference between all groups (P < 0.001). When compared with the control group (G1), the mean apoptotic cell count was fivefold that of G2 and 35- and 351-fold those of G3 and G4, respectively. Our study demonstrated that hyperoxaluria with complete ureteral obstruction induces an excessive level of apoptosis, which is responsible for renal damage, and that ureteral obstruction is a more important factor for apoptosis than hyperoxaluria. Considering these data, we also believe that research studies for medical preventive measures must be considered for patients with ureteral obstruction and/or hyperoxaluria.

Requirement of analgesia for extracorporeal shock wave lithotripsy and efficacy of a nonsteroidal antiinflammatory drug: piroxicam.

OBJECTIVE: In this study, the requirement of analgesia and the analgesic efficacy of a long-acting nonsteroidal antiinflammatory drug (NSAID), piroxicam, were investigated in patients with renal stone disease treated with extracorporeal shock wave lithotripsy (ESWL). METHODS: This randomized, placebo-controlled study included 60 patients. Patients were divided into two groups randomly. A single dose of saline (2 ml) was given to the patients in group 1 (n = 20) and 2 ml of 40 mg piroxicam to the patients in group 2 (n = 40). All injections were administered into the gluteal muscle 45 min before ESWL. A verbal rating scale (VRS) was used to evaluate the pain. Groups were compared according to age, sex, weight, height, stone size, number of shock waves, duration of ESWL and VRS scores. RESULTS: There was no statistically significant difference between both groups in demographic data, stone size, number of shock waves and duration of ESWL procedure (p > 0.05). However mean VRS scores were significantly lower in group 2 than in group 1 during and after the ESWL procedure. CONCLUSION: We considered that analgesic agents should be used to control the pain in second-generation lithotriptors. Piroxicam has clinically significant effects on the pain and also antiinflammatory effects, inhibits ureteric activity, and helps in stone passage.

Open surgical exploration after failed endopyelotomy: a 12-year perspective.

PURPOSE: Factors that have a role in endopyelotomy failure have not been fully elucidated but are believed to include high grade hydronephrosis and the presence of crossing vessels at the ureteropelvic junction. MATERIALS AND METHODS: We retrospectively analyzed the importance of renal function, hydronephrosis, ureteral stents, surgeon experience and crossing vessels in determining the outcome of endopyelotomy. RESULTS: Of 401 percutaneous antegrade endopyelotomies performed at our medical center during the last 12 years 60 failed and 54 of these patients underwent surgical exploration. Patients with high grade hydronephrosis and poor initial renal function were much less likely to have successful endopyelotomy than those with moderate hydronephrosis or good renal function (success rates 50 versus 96 and 54 versus 92%, respectively, p <0.001). The most common findings at exploration included severe extrinsic fibrosis and intrinsic fibrotic stenosis. Obstructing crossing vessels were present in 13 patients explored, suggesting a possible role in causing failure in only 4% of all endopyelotomy patients. CONCLUSIONS: Patients with high grade hydronephrosis and poor initial renal function are much more likely to experience endopyelotomy failure. Crossing vessels appear to have a less significant role in endopyelotomy failure than has been previously suggested.

Inhibition of calcium oxalate urolithiasis in a rat model of lithogenesis using bisphosphonates.

Bisphosphonates bind renal calculi and inhibit calcium oxalate crystal growth in vitro. We evaluated their ability to inhibit calcium oxalate urolithiasis in a lithogenic rat model. Male Sprague-Dawley rats (four groups, eight rats each) were fed 1.0% ethylene glycol in their drinking water for 6 weeks. All rats had implantation of a 50- to 60-mg zinc pellet in their urinary bladder at the beginning of the 6-week period. The control group received no treatment. The other three groups received six weekly intraperitoneal injections of one of three bisphosphonates: pamidronate (APD), clodronate (CLO), or methylene diphosphonate (MDP). At the end of 6 weeks, the zinc pellet was retrieved and weighed; the kidneys were sectioned and stained to evaluate inflammation, tubular dilation, and crystal deposition; and blood and urine samples were analyzed for calcium and creatinine. There were no detectable biochemical differences between the control and the treatment groups. Zinc pellets removed from control animals had a significantly greater increase in weight secondary to crystal deposition than those from the treatment groups (mean 28.4% for control v 18.9%, 15.3%, and 18.6%, respectively, for animals given APD, CLO, and MDP). The control animals also had significantly higher scores for inflammation, tubular dilation, and crystal deposition than animals treated with MDP and CLO. Older and newer-generation bisphosphonates have an inhibitory effect on calcium oxalate urolithiasis that is demonstrable at relatively infrequent dosing intervals in vivo. More frequent dosing or higher doses may allow greater inhibition of stone formation.