Surgical interventions for nephrolithiasis in ankylosing spondylitis and the general population.

OBJECTIVE: The aim of this study was to estimate rates and type of definitive surgical interventions for nephrolithiasis in Swedish patients with ankylosing spondylitis (AS) compared to the general population. MATERIALS AND METHODS: This national prospective cohort study linked data from Swedish population and healthcare registries. Incidence rates and interventions for nephrolithiasis during follow-up in patients with AS were compared to general population comparator (GPC) subjects. RESULTS: In total, 8572 AS patients were followed for 49,959 person-years and 39,639 matched GPCs were followed for 225,221 person-years. Mean age at study entry was 46 years [interquartile range (IQR) 36-56 years] and 65% were male. In AS patients with a diagnosis of nephrolithiasis during the study period, 29% (72/250) underwent similar intervention for nephrolithiasis compared to 24% (114/466) GPCs (p = 0.21). The incidence rate ratio (RR) in overall AS patients was 2.9 [95% confidence interval (CI) 2.1-3.8] during a median follow-up of 6.2 years (IQR 3.2-8.6 years). With prior diagnosis of nephrolithiasis, the RR for AS patients compared to GPCs was 3.7 (95% CI 1.8-7.7); without prior nephrolithiasis the RR was 2.1 (95% CI 1.5-3.0). Increasing age [odds ratio (OR) 1.02, 95% CI 1.01-1.03], prior nephrolithiasis diagnosis (OR 3.3, 95% CI 1.97-5.62) and atherosclerotic cardiac disease (OR 2.0, 95% CI 1.03-3.91) were identified as predictors of intervention for nephrolithiasis. CONCLUSIONS: Patients with AS have an almost three-fold increased risk of surgical intervention for kidney stones, with similar management, compared to the general population.

A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.

Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.

Dual-energy CT for the characterization of urinary calculi: In vitro and in vivo evaluation of a low-dose scanning protocol.

The efficiency and radiation dose of a low-dose dual-energy (DE) CT protocol for the evaluation of urinary calculus disease were evaluated. A low-dose dual-source DE-CT renal calculi protocol (140 kV, 46 mAs; 80 kV, 210 mAs) was derived from the single-energy (SE) CT protocol used in our institution for the detection of renal calculi (120 kV, 75 mAs). An Alderson-Rando phantom was equipped with thermoluminescence dosimeters and examined by CT with both protocols. The effective doses were calculated. Fifty-one patients with suspected or known urinary calculus disease underwent DE-CT. DE analysis was performed if calculi were detected using a dedicated software tool. Results were compared to chemical analysis after invasive calculus extraction. An effective dose of 3.43 mSv (male) and 5.30 mSv (female) was measured in the phantom for the DE protocol (vs. 3.17/4.57 mSv for the SE protocol). Urinary calculi were found in 34 patients; in 28 patients, calculi were removed and analyzed (23 patients with calcified calculi, three with uric acid calculi, one with 2,8-dihyxdroxyadenine-calculi, one patient with a mixed struvite calculus). DE analysis was able to distinguish between calcified and non-calcified calculi in all cases. In conclusion, dual-energy urinary calculus analysis is effective also with a low-dose protocol. The protocol tested in this study reliably identified calcified urinary calculi in vivo.

[Diagnostic procedures in upper urinary tract urothelial carcinoma]. / Diagnostik von Urothelkarzinomen des oberen Harntrakts.

Upper urinary tract transitional cell carcinomas represent 5-6% of all urothelial carcinomas. Macroscopic hematuria is the most common symptom. The diagnostic algorithm contains medical history, clinical investigation, cystoscopy, urinary cytology, ultrasound and intravenous urography. When suspected, a complementary retrograde pyeloureterography with collecting selective urinary cytology is conducted. When radiological findings are doubted or when conservative treatment is planned, an ureterorenoscopy for biopsy of the suspected area is indicated. Computed tomography and magnetic resonance tomography is used to define the local extension of invasive tumors and to detect metastases. The use of urinary markers in the diagnosis of upper urinary tract urothelial carcinoma has to be evaluated in prospective trials.

Hypertension accelerates the pace of chronic graft dysfunction in the rat.

In this study we compared the effects of hypertension on chronic rejection in a rat model of renal transplantation utilizing genetically normotensive (BBOK) and spontaneously hypertensive rats (SHR). SHR received either a BBOK (BBOK-->SHR) or an SHR (SHR-->SHR) kidney; normotensive isografts served as controls. Before transplantation, SHR recipients were treated with hydralazine (50 mg/kg per day). To prevent acute rejection, an anti-CD4 antibody (3 mg/kg per day for 3 weeks) in combination with cyclosporin A (3 mg/kg per day for 1 week) was given to all groups. Six weeks after transplantation, blood pressure was measured, and the kidneys removed for histological and immunohistological analysis. SHR-->SHR developed a significantly higher blood pressure than BBOK-->SHR. Blood pressure in BBOK-->BBOK was significantly lower than in the other two groups. The degree of glomerulosclerosis was similarly increased in allografted (BBOK-->SHR) and SHR-->SHR kidneys as compared with the BBOK-->BBOK kidneys (P < 0.05). Infiltration of ED-1+ monocyte/macrophages and OX19 pan-T-cells was most pronounced in allografts (BBOK-->SHR) and was also increased in SHR-->SHR as compared with BBOK-->BBOK. Our results indicate that hypertension accelerates the morphological and immunohistological changes characteristic of grafts undergoing chronic rejection. However, our findings support the hypothesis that alloantigen-dependent factors are of greater important.

Kidneys from normotensive donors lower blood pressure in young transplanted spontaneously hypertensive rats.

Single transplanted kidneys from spontaneously hypertensive rats (SHR) have been shown to elicit hypertension in genetically normotensive recipients. This study was designed to investigate the effects of single transplanted kidneys from genetically normotensive donors [Biobreeding (BB)/Ottawa Karlsburg (OK) rats] on blood pressure in SHR recipients. The following groups were formed: group 1 (n = 11), SHR donors and SHR recipients; group 2 (n = 15), BB/OK donors and SHR recipients; and group 3 (n = 8), BB/OK donors and BB/OK recipients. Recipients received antihypertensive treatment (hydralazine) from weaning until renal transplantation at the age of 9 wk and immunosuppressive treatment (anti-CD4 antibody and cyclosporine A) for 3 wk starting on the day of transplantation. Six weeks after transplantation, intra-arterially measured blood pressure and heart weight-to-body weight ratio were highest in group 1, intermediate in group 2, and lowest in group 3. There were no significant differences with respect to plasma urea and creatinine concentrations among the three groups. These results support the hypothesis that hypertension in renal-transplanted SHR depends in part on the genetic background of the transplanted kidney.

The importance of the kidney in primary hypertension: insights from cross-transplantation.

Experimental renal cross-transplantation studies with genetically hypertensive and normotensive rats have shown that hypertension travels with the kidney. The underlying mechanisms are currently not well understood. Genetically normotensive recipients of a kidney from spontaneously hypertensive rats show a decreased capacity to excrete sodium when challenged with a high-salt diet. Furthermore, they retain more sodium than recipients of a kidney from genetically normotensive donors immediately after transplantation and removal of the native kidneys. Sodium retention precedes hypertension and may contribute to its development. Most recently, it has been shown that bilateral nephrectomy and transplantation of a genetically normotensive kidney attenuates the development of hypertension in young transplanted spontaneously hypertensive rats. Thus, long-term blood pressure in renal transplanted rats is critically determined by the genetic background of the renal graft. Together, these data indicate that genetically determined renal mechanisms play a major role in primary hypertension.