Alternate or additional findings to stone disease on unenhanced computerized tomography for acute flank pain can impact management

PURPOSE: We evaluated the incidence and clinical relevance of alternate or additional findings on unenhanced CT in patients with acute flank pain and suspected urinary calculi. MATERIALS AND METHODS: A consecutive series of 1,500 patients underwent unenhanced CT due to acute flank pain. The absence or presence of urinary tract calculi and their localization were recorded. Alternate or additional CT findings were classified according to whether they required immediate or deferred treatment, or were of little or no clinical importance. RESULTS: Of the 1,500 patients 1,035 (69%) had urinary tract calculi, including 309 (30%) with nephrolithiasis, 377 (36%) with ureterolithiasis and 349 (34%) with the 2 conditions. Urolithiasis alone was found in 331 of these patients (32%) and additional pathological conditions were noted in 704 (68%). Of all patients 1,064 (71%) had other or additional CT findings. Of all patients 207 (14%) had nonstone related CT findings requiring immediate or deferred treatment, 464 (31%) had pathological conditions of little clinical importance and 393 (26%) had pathological conditions of no clinical relevance. CT was normal in 105 of all patients (7%). CONCLUSIONS: Unenhanced CT in patients with acute flank pain allows the accurate diagnosis of urinary stone disease and it can also provide further important information leading to emergency or deferred treatment in a substantial number of patients.

Does Stepwise Voltage Ramping Protect the Kidney from Injury During Extracorporeal Shockwave Lithotripsy? Results of a Prospective Randomized Trial

BACKGROUND Renal damage is more frequent with new-generation lithotripters. However, animal studies suggest that voltage ramping minimizes the risk of complications following extracorporeal shock wave lithotripsy (SWL). In the clinical setting, the optimal voltage strategy remains unclear. OBJECTIVE To evaluate whether stepwise voltage ramping can protect the kidney from damage during SWL. DESIGN, SETTING, AND PARTICIPANTS A total of 418 patients with solitary or multiple unilateral kidney stones were randomized to receive SWL using a Modulith SLX-F2 lithotripter with either stepwise voltage ramping (n=213) or a fixed maximal voltage (n=205). INTERVENTION SWL. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was sonographic evidence of renal hematomas. Secondary outcomes included levels of urinary markers of renal damage, stone disintegration, stone-free rate, and rates of secondary interventions within 3 mo of SWL. Descriptive statistics were used to compare clinical outcomes between the two groups. A logistic regression model was generated to assess predictors of hematomas. RESULTS AND LIMITATIONS Significantly fewer hematomas occurred in the ramping group(12/213, 5.6%) than in the fixed group (27/205, 13%; p=0.008). There was some evidence that the fixed group had higher urinary β2-microglobulin levels after SWL compared to the ramping group (p=0.06). Urinary microalbumin levels, stone disintegration, stone-free rate, and rates of secondary interventions did not significantly differ between the groups. The logistic regression model showed a significantly higher risk of renal hematomas in older patients (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05; p=0.04). Stepwise voltage ramping was associated with a lower risk of hematomas (OR 0.39, 95% CI 0.19-0.80; p=0.01). The study was limited by the use of ultrasound to detect hematomas. CONCLUSIONS In this prospective randomized study, stepwise voltage ramping during SWL was associated with a lower risk of renal damage compared to a fixed maximal voltage without compromising treatment effectiveness. PATIENT SUMMARY Lithotripsy is a noninvasive technique for urinary stone disintegration using ultrasonic energy. In this study, two voltage strategies are compared. The results show that a progressive increase in voltage during lithotripsy decreases the risk of renal hematomas while maintaining excellent outcomes. TRIAL REGISTRATION ISRCTN95762080.

The Vacuolar H+-ATPase B1 Subunit Polymorphism p.E161K Associates with Impaired Urinary Acidification in Recurrent Stone Formers

Mutations in the vacuolar–type H+-ATPase B1 subunit gene ATP6V1B1 cause autosomal–recessive distal renal tubular acidosis (dRTA). We previously identified a single-nucleotide polymorphism (SNP) in the human B1 subunit (c.481G.A; p.E161K) that causes greatly diminished pump function in vitro. To investigate the effect of this SNP on urinary acidification, we conducted a genotype-phenotype analysis of recurrent stone formers in theDallas and Bern kidney stone registries. Of 555 patients examined, 32 (5.8%) were heterozygous for the p.E161K SNP, and the remaining 523 (94.2%) carried two wild–type alleles. After adjustment for sex, age, body mass index, and dietary acid and alkali intake, p.E161K SNP carriers had a nonsignificant tendency to higher urinary pH on a random diet (6.31 versus 6.09; P=0.09). Under an instructed low–Ca and low–Na diet, urinary pH was higher in p.E161K SNP carriers (6.56 versus 6.01; P,0.01). Kidney stones of p.E161K carriers were more likely to contain calcium phosphate than stones of wild-type patients. In acute NH4Cl loading, p.E161K carriers displayed a higher trough urinary pH (5.34 versus 4.89; P=0.01) than wild-type patients. Overall, 14.6% of wild-type patients and 52.4% of p.E161K carriers were unable to acidify their urine below pH 5.3 and thus, can be considered to have incomplete dRTA. In summary, our data indicate that recurrent stone formers with the vacuolar H+-ATPase B1 subunit p.E161K SNP exhibit a urinary acidification deficit with an increased prevalence of calcium phosphate– containing kidney stones. The burden of E161K heterozygosity may be a forme fruste of dRTA.

Variability in urinary oxalate measurements between six international laboratories

Hyperoxaluria is a major risk factor for kidney stone formation. Although urinary oxalate measurement is part of all basic stone risk assessment, there is no standardized method for this measurement.

Recombinant major urinary proteins of the mouse in specific IgE and IgG testing

Background: Recombinant allergens are preferred over natural allergen extracts in measuring antibodies. We tested the use of recombinant variants of the major mouse allergen Mus m 1 in detection of mouse-specific antibodies in sera of laboratory animal workers and children. Methods: Six recombinant major urinary proteins (MUPs) were produced and antibody-binding capacity was compared to natural Mus m 1 and to mouse urine extract. In a specific subset, cross-reactivity of MUP with Mus m 1 and between the different recombinant MUPs was determined. Results: For IgE antibodies, MUP8 showed high cross-reactivity with Mus m 1. MUP8-specific IgE was found in 55% of the mouse urine IgE-positive sera. Specific IgG and IgG4 antibodies against natural Mus m 1 correlated strongly with antibodies against recombinant MUP8 and were cross-reactive. IgG4 levels against MUP8 and mouse urine extract correlated, but detection of mouse urine-specific IgG4 in the absence of MUP-specific IgG4 was not uncommon. Cross-reactivity of IgG antibodies between MUP8 and Mus m 1 as well as between the different MUPs was high and inhibition varied between 54 and 99%. Conclusion: The mouse allergen Mus m 1 can be replaced in antibody testing by recombinant MUP8. Other MUPs, except MUP4, are interchangeable with MUP8. However, mouse urine extract showed better detection of both mouse-specific IgE and IgG4 levels. Other components in the mouse urine, like mouse albumin and other yet unidentified components, also induce IgE and IgG(4) antibodies.

Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation

The rate-limiting step of dietary calcium absorption in the intestine requires the brush border calcium entry channel TRPV6. The TRPV6 gene was completely sequenced in 170 renal calcium stone patients. The frequency of an ancestral TRPV6 haplotype consisting of three non-synonymous polymorphisms (C157R, M378V, M681T) was significantly higher (P = 0.039) in calcium stone formers (8.4%; derived = 502, ancestral = 46) compared to non-stone-forming individuals (5.4%; derived = 645, ancestral = 37). Mineral metabolism was investigated on four different calcium regimens: (i) free-choice diet, (ii) low calcium diet, (iii) fasting and (iv) after a 1 g oral calcium load. When patients homozygous for the derived haplotype were compared with heterozygous patients, no differences were found with respect to the plasma concentrations of 1,25-vitamin D, PTH and calcium, and the urinary excretion of calcium. In one stone-forming patient, the ancestral haplotype was found to be homozygous. This patient had absorptive hypercalciuria. We therefore expressed the ancestral protein (157R+378V+681T) in Xenopus oocytes and found a significantly enhanced calcium permeability when tested by a (45)Ca(2+) uptake assay (7.11 +/- 1.93 versus 3.61 +/- 1.01 pmol/min/oocyte for ancestral versus derived haplotype, P < 0.01). These results suggest that the ancestral gain-of-function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria.

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein profiling of organic stone matrix and urine from dogs with urolithiasis

Two-thirds of the organic matrix in urinary stones consists of proteins. Their relationship to calculogenesis remains controversial with regard to their effect as inhibitors or promoters during stone formation. The purpose of the present study was to determine the differences in peptide and protein pattern between the urine of stone formers (n = 23) and control dogs (n = 12), as well as between organic matrix of different urinary stones (struvite n = 11, calcium oxalate n = 8, uric acid n = 4) using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Specific differences in protein and peptide profiles were found in the organic matrix of different mineral compositions. Characteristic differences were also found in urinary peptide and protein pattern especially in molecular masses below 20 kDa between affected and healthy dogs. Based on the obtained molecular masses they were in some cases tentatively identified as proteins that are known to be involved in stone formation in humans. The study shows that in dogs, specific-urinary peptides and proteins might be associated with urolithiasis. It indicates the importance to further characterize those proteins for possible diagnostic purposes in prognosis and therapy

Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge

Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3alpha,6,7alpha,12alpha-tetrol (3alpha,6,7alpha,12alpha-tetrahydroxy-5beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.

Real-time polymerase chain-reaction detection of pathogens is feasible to supplement the diagnostic sequence for urinary tract infections

To evaluate, in a prospective pilot study, the feasibility of identifying pathogens in urine using real-time polymerase chain reaction (PCR), and to compare the results with the conventional urine culture-based procedures.

Effects of thoracic epidural analgesia on lower urinary tract function in women

The need for an indwelling transurethral catheter in patients with postoperative thoracic epidural analgesia (TEA) is a matter of controversy. Subjective observations are ambivalent and the literature addressing this issue is scarce. As segmental blockade can be achieved with epidural analgesia, we hypothesized that analgesia within segments T4-T11 has no or minimal influence on lower urinary tract function. Thus, we evaluated the effect of TEA on lower urinary tract function by urodynamic studies.

The role of exenterative surgery and urinary diversion in persistent or locally recurrent gynecological malignancy: complications and survival

Treatment options in patients with persistent or locally recurrent cervical cancer are limited. The aim of this study was to determine the chance of cure and associated morbidity following pelvic exenteration.

Identification of noninvasive biomarkers for alcohol-induced liver disease using urinary metabolomics and the Ppara-null mouse

Alcohol-induced liver disease (ALD) is a leading cause of nonaccident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively nonspecific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study, the metabolic changes associated with ALD were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-beta-d-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of a metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model.

Urinary proteomics before and after extracorporeal circulation in patients with and without acute kidney injury

Acute kidney injury is a well-known complication with high morbidity and mortality after cardiopulmonary bypass. Cardiopulmonary bypass-associated acute kidney injury is still poorly understood.

Mapping of a new locus for congenital anomalies of the kidney and urinary tract on chromosome 8q24

Congenital anomalies of the kidney and urinary tract (CAKUT) account for the majority of end-stage renal disease in children (50%). Previous studies have mapped autosomal dominant loci for CAKUT. We here report a genome-wide search for linkage in a large pedigree of Somalian descent containing eight affected individuals with a non-syndromic form of CAKUT.