Masanori Iguchi

Prevalence and Epidemiological Characteristics of Urolithiasis in Japan: National Trends Between 1965 and 2005

OBJECTIVES We evaluated the epidemiological details and chronological trends of upper urinary tract stones in Japan using a nationwide survey of urolithiasis. METHODS All patient visits to urologists that resulted in a diagnosis of first-episode upper urinary tract stones in 2005 were enumerated irrespective of admission and treatment. The study included all hospitals approved by the Japanese Board of Urology, thus covering nearly all urologists practicing in Japan. We compared the estimated annual incidence according to gender and age with the incidence determined from nationwide surveys between 1965 and 1995. RESULTS The estimated annual incidence of first-episode upper urinary tract stones in 2005 was 134.0 per 100,000 (192.0 in men and 79.3 in women). The estimated age-standardized annual incidence of first-episode upper urinary tract stones in 2005 was 114.3 per 100,000 (165.1 for men and 65.1 for women), which represents a steady increase from 54.2 in 1965. The annual incidence has increased in all age groups except during the first 3 decades of life and the peak age for both men and women has also increased. CONCLUSIONS The annual incidence of upper urinary tract stones has steadily increased in Japan and this trend will continue in the near future. This probably results from improvements in clinical-diagnostic procedures, changes in nutritional and environmental factors, and general apathy toward metabolic clarification and metaphylaxis.

Molecular cloning and sequencing of cDNA encoding urinary stone protein, which is identical to osteopontin

We have sequenced a cDNA of urinary stone protein. cDNA sequences show complete homology between urinary stone protein and human osteopontin (bone sialoprotein) (nucleotides 265-886 and 1183-1424). Osteopontin is a recently discovered bone matrix protein which has been implicated in mediating mineral formation within bone extracellular matrix. This result shows that osteopontin is presumably involved in stone formation as stone matrix.

Association of Metabolic Syndrome Traits and Severity of Kidney Stones: Results From a Nationwide Survey on Urolithiasis in Japan

BACKGROUND Although metabolic syndrome and its individual components have been associated with kidney stone disease, whether the clustering of metabolic syndrome traits increases the severity of kidney stone disease has not been examined in a large-scale study. STUDY DESIGN Cross-sectional analysis. SETTING & PARTICIPANTS Data were obtained from 30,448 patients enrolled in the 6th Nationwide Survey on Urolithiasis in Japan conducted in 2005. Patients with lower urinary tract stones, struvite stones, cystine stones, or hyperparathyroidism and those younger than 15 years were excluded. PREDICTOR Number of metabolic syndrome traits (obesity [body mass index ≥25 kg/m(2)], diabetes, hypertension, and dyslipidemia). OUTCOMES Severe form of kidney stone disease, defined as recurrent and/or multiple stones, and abnormalities in urine constituents (hypercalciuria, hyperuricosuria, hyperoxaluria, and hypocitraturia). RESULTS 11,555 patients were included in the final analyses. Proportions of patients with recurrent and/or multiple stones were 57.7%, 61.7%, 65.2%, 69.3%, and 73.3% with 0, 1, 2, 3, and 4 metabolic syndrome traits, respectively (P < 0.001). There was a significant and stepwise increase in the odds of recurrent and/or multiple stones after adjustment for age and sex. In patients with 4 metabolic syndrome traits, the odds was 1.8-fold greater compared with patients with 0 traits (OR, 1.78; 95% CI, 1.22-2.66). In addition, the presence of metabolic syndrome traits was associated with significantly increased odds of having hypercalciuria, hyperuricosuria, hyperoxaluria, and hypocitraturia after adjustment for age and sex. LIMITATIONS Cross-sectional design, absence of dietary data, ill-defined diagnostic criteria for metabolic syndrome traits, and missing data for the majority of participants. CONCLUSIONS Metabolic syndrome trait clustering is associated with greater severity of kidney stone disease; increased urinary calcium, uric acid, and oxalate excretion; and decreased urinary citrate excretion. These results suggest that kidney stone disease should be regarded as a systemic disorder linked to metabolic syndrome.

The effect of osteopontin on the adhesion of calcium oxalate crystals to Madin-Darby canine kidney cells

OBJECTIVE We have recently reported that osteopontin protein (OPN) is present in calcium-containing urinary calculi and in rat distal tubular cells and that it is an important substance of the matrix in urinary stone formation. To investigate how OPN participates in urinary stone formation, we assessed the role of OPN in the adhesion of the surfaces of Madin-Darby canine kidney (MDCK) cells, which are distal tubular cells of the dog, to calcium oxalate crystals. METHODS We cultured MDCK cells with OPN, thrombin, which is an OPN inhibitor, Arg-Gly-Asp peptide and Arg-Gly-Glu peptide as a control for Arg-Gly-Asp peptide, and examined changes in adhesion of calcium oxalate crystals to the cells by scanning electron microscopy and the calcium (45Ca) concentration around the cells. RESULTS The 45Ca concentration in calcium oxalate crystals adhering to MDCK cells was about 1.4 times higher in MDCK cells incubated with OPN than in an MDCK-cell-negative group, and was about one half that in MDCK cells incubated with thrombin than in the group without MDCK cells. CONCLUSION OPN is considered to be an accelerator of urinary stone formation because of the increase in adhesion of calcium oxalate crystals to the renal distal tubular epithelium in the presence of OPN. These findings suggest that OPN plays an important role in the formation of calcium-containing urinary stones.

Interaction between Osteopontin on Madin Darby Canine Kidney Cell Membrane and Calcium Oxalate Crystal

We recently reported that the addition of the protein osteopontin (OPN) resulted in an increase in the deposition of calcium oxalate (CaOx) crystals on the surface of Madin Darby canine kidney (MDCK) cells. To determine the degree to which this increased deposition is caused by OPN, we investigated the extent to which the CaOx crystal deposition produced by the expression of OPN at the cell surface was suppressed by 4 different methods prior to the determination of the level of CaOx crystal binding. MDCK cells (2 × 106 cells/well) were cultured to a confluent state, and the binding of OPN to the cellular surface was then inhibited by adding one of the following 4 substances: human OPN polyclonal antibody, thrombin, cyclic Arg-Gly-Asp (RGD) peptides and tunicamycin. The cells were cultured for 24 h. We then used a fluorescent antibody technique with an OPN polyclonal antibody to determined whether the expression of OPN at the cell surface was inhibited, and we measured the degree of CaOx crystal deposition using the isotope 45Ca. The degree of CaOx crystal deposition was inhibited by 80% or more in the antibody-treated group, by 50–80% in the thrombin-treated group, by 60–80% in the cyclic RGD-treated group, and by 50–60% in the tunicamycin-treated group. These results suggest that OPN in the extracellular matrix is the main cause of CaOx crystal deposition on the surface of MDCK cells.

The Role of Osteopontin on Calcium Oxalate Crystal Formation

OBJECTIVE We evaluated whether osteopontin (OPN) and other proteins with the RGD sequence as in OPN (RGD family proteins) that are present in renal tubular cells (fibronectin [FN], Tamm-Horsfall glycoprotein [THP], vitronectin [VN], and laminin [LN]) inhibit the aggregation and growth of calcium oxalate (CaOx) crystals by a novel seed crystal method using collagen granules (CG) with and without OPN adhered on the surface. We also evaluated the effect of solid phase OPN, FN and THP in which the relationship between their proteins and CaOx crystallization was reported. Moreover, the state and time-course changes in CaOx crystals adhered to CG were observed under scanning electron microscopy (SEM). METHODS The inhibitory activity (IA) on the aggregation and growth of CaOx crystals was measured in vitro by the conventional seed crystal method using isotopes. In this study, the following nine samples were used: OPN alone; FN alone; THP alone; VN alone; LN alone; CG alone; and CG with OPN, FN, or THP adhered on the surface (OPN/FN/THP-immobilized CG). In addition, the state and time-course changes in CaOx crystals adhered to CG were evaluated by SEM. RESULTS Using the conventional seed crystal method, the following values of IA were obtained: 91.7% (37.5 micro g/ml) for OPN, 5.0% (100 micro g/ml) for FN, 2.0% (100 micro g/ml) for THP, 3.0% (100 micro g/ml) for VN, and 1.0% (100 micro g/ml) for LN. However, the value of IA obtained by our seed crystal method using CG was 92.1% (180cm(2)/5ml PBS) when CG alone was used. Although the value of IA was decreased by 33.6% when OPN-immobilized CG was used, it did not significantly change when FN/THP-immobilized CG was used. When CG alone was used, the evaluation of CaOx crystallization by SEM demonstrated mild adherence and aggregation of CaOx crystal suspension (seed crystals) on the CG surface, although newly formed crystals only slightly adhered to the CG surface. When OPN-immobilized CG was used, marked adherence and aggregation of seed crystals were observed, in addition to the relatively increased adherence of newly formed crystals. When FN/THP-immobilized CG was used, newly formed crystals only slightly adhered to the CG surface, although the degree of seed crystal adherence and aggregation did not significantly change. CONCLUSIONS These findings suggest that the immobilization of OPN to the CG surface enhances the adherence and aggregation of seed crystals, as well as enhancing the adherence of newly formed crystals, resulting in decreased IA of CG (overall promotion of crystal deposition). Therefore, the results of this study clarified that OPN enhances the formation and aggregation of CaOx crystals in this experimental system.

Comparison of imaging methods for localization of parathyroid tumors

Preoperative localization of parathyroid tumors by computed tomography (CT), thallium-201/technetium-99m pertechnetate subtraction scintigraphy (Tl-201/Tc-99m), ultrasonography (US), and magnetic resonance imaging (MRI) was compared in patients with hyperparathyroidism (HPT) to examine the characteristics of each method. A total of 87 patients with HPT were divided into two groups according to the time when they were examined. Patients in group I were examined before MRI had been introduced in our hospital, and a 2.5-MHz transducer probe was used for US. Those in group II were examined by MRI and US using a 7.5-MHz transducer probe. Group I included 45 patients (36 with primary hyperparathyroidism [PHPT] and 9 with secondary hyperparathyroidism [SHPT]), and group II included 42 patients (15 with PHPT and 27 with SHPT). In both PHPT and SHPT and SHPT of group I and PHPT of group II, there was no significant difference in detection rates between all diagnostic methods. In patients with SHPT in group II, the detection rate was significantly higher for CT than for Tl-201/Tc-99m and MRI (both p less than 0.01), and for US than for Tl-201/Tc-99m (p less than 0.01). In both groups I and II, the detection rate of each study method was significantly higher in patients with PHPT than in those with SHPT (all p less than 0.01). Compared with group I, the rate was significantly improved in group II, in both types of patients. Regarding the location of the parathyroid tumor, the detection rate of CT was significantly higher for upper parathyroid glands than for lower glands, whereas that of US and Tl-201/Tc-99m was significantly higher for lower glands. The detection rate sharply increased when the tumor weight reached 250 mg (CT, US) or 1,000 mg (Tl-201/Tc-99m, MRI).

The effect of takusha, a kampo medicine, on renal stone formation and osteopontin expression in a rat urolithiasis model.

Abstract Kampo medicine is a traditional Japanese therapeutic system which originated in China and was used to treat various diseases for hundreds of years. Kampo medicine had been also used for the cure and the prevention of urinary calculi for many years, but the effect and the mechanism of this use of kampo medicine are unclear. We examined the inhibitory effect of the kampo medicine takusha on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) and vitamin D3 in rats. We also investigated the effect of takusha on osteopontin (OPN) expression, which we previously identified as an important stone matrix protein. The control group rats were non-treated; the stone group rats were administered EG and vitamin D3, and the takusha group was administered takusha in addition to EG and vitamin D3. The rate of renal stone formation was lower in the takusha group than in the stone group; thus, the OPN expression in the takusha group was smaller than in the stone group. Takusha was effective in preventing oxalate calculi formation and OPN expression in rats. These findings suggest that takusha prevents stone formation including not only calcium oxalate aggregation but also proliferation.

Randomized trial of trigger point injection for renal colic

Abstract Background: Many drugs have been utilized for the treatment of renal colic, but to date no drugs that relieve pain quickly and completely have been developed. Thus, we conducted a prospective trial to evaluate the effects of trigger point injection on renal colic. In this study, we used a local injection of lidocaine to the trigger point of patients experiencing renal colic, and evaluated the efficacy in patients using the visual analog scale.

Prevalence of Urolithiasis in Kaizuka City, Japan—An Epidemiologic Study of Urinary Stones

Background: According to the results of nationwide surveys, the prevalence of urolithiasis has been steadily increasing in Japan. However, these surveys relied on hospital statistics, and there has been no survey of the prevalence of urolithiasis in Japan utilizing postal questionnaires. We surveyed the prevalence of urolithiasis among the inhabitants of Kaizuka City.