Neutrophil-to-lymphocyte ratio but not monocyte-to-HDL cholesterol ratio nor platelet-to-lymphocyte ratio correlates with early stages of lower extremity arterial disease: an ultrasonographic study.

OBJECTIVE: The role of inflammatory markers as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-high-density lipoprotein-cholesterol ratio (MHR), and platelet-to-lymphocyte ratio (PLR) in cardiovascular diseases has been widely investigated in recent years. In the context of lower extremity arterial disease (LEAD), this association has been mainly studied in the advanced stages. The aim of our study was to investigate the role of these inflammatory markers in all stages of LEAD, including early ones, using ultrasonography as diagnostic tool, together with ankle-brachial index (ABI) determination. PATIENTS AND METHODS: In this cross-sectional observational study, we enrolled 240 patients undergoing ultrasonographic evaluation of the lower limb arteries and ABI determination because of symptoms suggestive of LEAD or presence of known cardiovascular risk factors. RESULTS: In our study population, we found that ultrasonographic categories of LEAD were associated with NLR, but not with MHR and PLR. CONCLUSIONS: These results confirm that a specific pattern of inflammation can be found in all stages of LEAD, including early ones.

Angiosarcoma of an Arteriovenous Fistula for Hemodialysis in a Kidney Transplant Recipient Affected by Lowe's Syndrome.

Objective/Background. To describe an uncommon, life-threatening condition such as angiosarcoma of a fistula for hemodialysis occurring in a transplant recipient affected by Lowe's syndrome. Summary. We present the case of a 56-year-old male kidney transplant recipient affected by Lowe's syndrome, also known as oculocerebrorenal syndrome, a rare X-linked disorder characterized by congenital cataracts, hypotonia, intellectual disability, and Fanconi-like renal tubular dysfunction, who was diagnosed with angiosarcoma of a functioning arteriovenous fistula for hemodialysis. Conclusion. Angiosarcoma is a rare soft tissue tumor, and only 22 cases of angiosarcoma of arteriovenous fistulae were described so far; although a correlation between Lowe's syndrome and a higher risk of tumor compared to the general population has not been described so far, the mechanisms of disease causation could be an interesting starting point for future studies on a possible connection between the two events.

Living kidney donation from people at risk of nephrolithiasis, with a focus on the genetic forms.

Deciding whether to accept a donor with nephrolithiasis is a multifaceted task because of the challenge of finding enough suitable donors while at the same time ensuring the safety of both donors and recipients. Until not long ago, donors with a history of renal stones or with stones emerging during screening on imaging were not considered ideal, but recent guidelines have adopted less stringent criteria for potential donors at risk of stones. This review goes through the problems that need to be approached to arrive at a wise clinical decision, balancing the safety of donors and recipients with the need to expand the organ pool. The risk of declining renal function and worsening stone formation is examined. Documents (consensus statements, guidelines, etc.) on this issue released by the most important medical societies and organizations are discussed and compared. Specific problems of living kidney donation associated with certain systemic (chronic hypercalcemia due to CYP24A1 gene mutations, primary hyperoxaluria, APRT deficiency) and renal (medullary sponge kidney, cystinuria, distal renal tubular acidosis, Dent's disease, Bartter syndrome, familial hypomagnesemia with hypercalciuria and nephrocalcinosis) Mendelian disorders that cause nephrolithiasis are also addressed.

Association between peripheral arterial disease and cardiovascular risk factors: role of ultrasonography versus ankle-brachial index.

OBJECTIVE: Most studies on atherosclerotic processes include peripheral arterial disease diagnosis only if patients report symptoms suggestive of peripheral arterial disease and/or an instrumental demonstration of lower limbs perfusion deficit is provided, rather than the sole presence of atherosclerotic lesions localized at lower limbs, this attitude leading to ignore early stages of the disease. To overcome these limitations, we have proposed a new ultrasonographic semiquantitative score to better identify all disease stages. The aim of this study is to compare ultrasonography versus ankle-brachial index in the association between peripheral arterial disease and cardiovascular risk factors. PATIENTS AND METHODS: This cross-sectional observational study included subjects undergoing lower limbs evaluation through ultrasonography and ankle-brachial index determination because of symptoms suggestive of peripheral arterial disease or presence of known cardiovascular risk factors. Associations between ultrasonography and ankle-brachial index with cardiovascular risk factors were assessed by first fitting logistic regression models and then comparing the respective areas under the Receiver Operating Characteristic and 95% confidence intervals. RESULTS: The areas under the Receiver Operating Characteristic for each cardiovascular risk factors were consistently larger in magnitude for ultrasonography compared with ankle-brachial index, this comparison being statistically significant for age, male gender, smoking status, hypertension, diabetes mellitus and previous cardiovascular events. CONCLUSIONS: Our study demonstrates that ultrasonography is a better method to screen peripheral arterial disease respect to ankle-brachial index in order to identify all disease stages. These findings are useful in particular when including peripheral arterial disease as organ damage marker in cardiovascular risk stratification.

Chronic pain in medullary sponge kidney: a rare and never described clinical presentation.

Medullary sponge kidney (MSK) is a cause of nephrocalcinosis, associated with hematuria, renal colic, pyelonephritis. There are rare and atypical MSK cases characterized by chronic severe pain (CP), whose features are unknown, in particular the relationship with the stone disease activity. This study analyzes a cohort of MSK-CP patients belonging to three North-America self-support Facebook groups. Patients had to self-administer an on-line questionnaire (on intensity, progression and MSK-associated conditions, stone-related disease, pain features, drug use), the Brief Pain Inventory, the Fatigue Severity Score, and Wisconsin Quality of Life (WQL) in stone formers questionnaires. Ninety-two patients with a diagnosis of MSK joined our survey. Stone rate was very high (3.1 stones per patient-year, < 15% of patients had ≤ 1 stone per year). Most patients had repeated hospitalizations for stones symptoms (p < 0.001) or pain (p < 0.005). 71% of participants referred a daily pain that interfered strongly with everyday life and quality of life (WQL mean value 29.4). 69% used pain medications daily (70% opioids). In most cases, pain was associated with stone passage, while 15% referred a sine materia pain. We showed how MSK-CP symptoms affect very negatively on the quality of life of these patients. They also have a definite risk of progressing to end-stage kidney disease. Generally, CP seems to be associated with an exceptionally high lithogenic activity, suggesting that a better and earlier metabolic treatment for stone prevention should be the first approach in these patients before mini-invasive treatments to prevent pain.

Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study.

BACKGROUND: Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti-TNF alpha. Patients with severe skin lesions unresponsive to topical therapy need to withdraw from treatment. AIM: To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti-TNF alpha and to analyse its clinical correlates. METHODS: A retrospective cohort study on all IBD patients who started anti-TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time-dependent predictors were updated at each available time point. RESULTS: Four hundred and two patients were included. Participants contributed a total of 839 person-years of follow-up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person-years. Cox-regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36-4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12-0.92; P = 0.03). CONCLUSIONS: Paradoxical psoriasis is a relevant side effect of anti-TNF alpha therapy, with an incidence rate of five per 100 person-years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti-TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.

A London experience 1995-2012: demographic, dietary and biochemical characteristics of a large adult cohort of patients with renal stone disease.

BACKGROUND: Kidney stone disease has an estimated prevalence of around 10%. Genetic as well as environmental factors are thought to play an important role in the pathogenesis of renal stones. AIM: The aim of our study was to analyse and report the main characteristics of patients with kidney stones attending a large UK metabolic stone clinic in London between 1995 and 2012. DESIGN: A cross-sectional study. METHODS: Analysis of data from stone formers attending the University College and Royal Free Hospitals' metabolic stone clinic from 1995 to 2012. Demographic, clinical, dietary and biochemical characteristics have been summarized and analysed for men and women separately; trends over time have also been analysed. RESULTS: Of the 2861 patients included in the analysis, 2016 (70%) were men with an average age of 47 years (range 18-87 years) and median duration of disease of 6 years (range 0-60 years). The prevalence of low urine volume, hypercalciuria, hyperoxaluria, hyperuricosuria and hypocitraturia was 5.6%, 38%, 7.9%, 18% and 23%, respectively. The prevalence of several risk factors for stones increased over time. The majority of stones were mixed, with around 90% composed of calcium salts in varying proportion. CONCLUSION: Our findings in a large cohort of patients attending a London-based stone clinic over the past 20 years show differences in distributions of risk factors for stones for men and women, as well as metabolic profiles and stone composition. The impact of most risk factors for stones appeared to change over time.

Temporal trend of cadmium exposure in the United States population suggests gender specificities.

BACKGROUND: Over the years, environmental cadmium exposure has been linked to increased mortality. Over the years, the use of cadmium has generally decreased. AIMS: Although even relatively low levels of cadmium have been associated with increased mortality in the general population, whether this applies to blood cadmium is not well understood. METHODS: The authors analysed data of the National Health and Nutrition Examination Survey to study the temporal trend of cadmium exposure in the period 1988-2006 and the risk of all-cause, cancer and cardiovascular mortality associated with blood cadmium levels. RESULTS: Urinary cadmium decreased significantly over time in males (0.58 (0.01) mcg/g to 0.41 (0.01) mcg/g; P < 0.001) but not in females (0.71 (0.09) mcg/g to 0.63 (0.08) mcg/g; P= 0.66). All-cause mortality was significantly higher in the highest quartiles compared with the lowest quartile of blood cadmium in both males (hazard ratio 1.89, 95% confidence interval 1.22, 2.89; P= 0.005) and females (hazard ratio 2.03, 95% confidence interval 1.06, 3.89; P= 0.035) after adjustment for age, race/ethnicity, smoke status, alcohol intake, annual household income and body mass index. There was also a significant association with cardiovascular mortality in females (P= 0.025). CONCLUSIONS: Our data show that elevated blood cadmium levels are associated with elevated mortality, that there seem to be gender differences in temporal trends of cadmium exposure and that blood cadmium is a proxy of chronic cadmium exposure.

Cytokines profile in serum of homozygous familial hypercholesterolemia is changed by LDL-apheresis.

OBJECTIVE: The effects of LDL-apheresis (LDLa) with dextran sulphate on plasma cytokines in 6 homozygous familial hypercholesterolemic (HozFH) patients, were evaluated. METHODS: Plasma IL-1α; IL-1ra; IL-4; IL-6; IL-10; IL-12(p40); IL-12(p70); TNF-α, sTNF-R, VEGF, VEGF-R1, E-Selectin (ESEL), and P-Selectin (PSEL) concentrations were measured before and after LDLa on three consecutive sessions for each patient. RESULTS: TNF-α was significantly reduced (-60%; P=0.01), while TNF-R was only slightly increased (+15%), although not significantly. Plasma VEGF was significantly reduced (-57%; P=1.87301E-05), while VEGF-R1 was significantly increased (+56%; P=0.05). ESEL and PSEL were reduced but not to a statistically significant extent (-19%, -15%, respectively). IL-1α level was dramatically reduced (-87%; P=0.0001). IL-1ra concentration was only slightly increased in plasma, but not significantly. IL-4 and IL-10 levels were significantly reduced in plasma after apheresis (-50%; P=0.03, and -55%; P=0.004, respectively). On the contrary, IL-6 concentration showed a slight decrease (-8%). Plasma IL-12p40 was significantly increased (+47%; P=0.0004). On the other hand, IL-12p70 was reduced, but the difference (-31%) was not statistically significant. CONCLUSIONS: Plasma cytokines imbalance is associated with inflammation and atherogenesis. In this study LDLa changed several circulating cytokines inducing anti-inflammatory and anti-atherogenic changes in cytokines plasma profile in HozFH patients with/without pre-existing angiographically demonstrated coronary heart disease (CHD) and aortic valvular disease (AVD).

Treatment of symptomatic hyperLp(a)lipidemia with LDL-apheresis vs. usual care.

BACKGROUND/AIMS: To assess LDL-apheresis efficacy to lower Lp(a) and to compare the effects of Usual Medical Care (UMC) a 12-months study was carried out. The incidence of new coronary artery disease (CAD) events/need of revascularization, was also monitored. METHODS: Twenty-one patients with hyperLp(a)lipidemia and angiographically documented CAD were randomly assigned to LDL-apheresis every week, or the UMC. RESULTS: LDL-apheresis group, averaged an Lp(a) reduction of 57.8+/-9.5% vs. basal values (P<0.001). In the UMC group Lp(a) increased in 1 year to 14.7+/-36.5% (P=0.66). Stepwise multivariate regression analysis for predictors of Lp(a) including: type of treatment, smoking, hypertension, age, age at first cardiovascular event, initial Lp(a), LDL, and BMI values, was performed. Only the type of treatment was co-related (P<0.001): Lp(a) variation (beta)=0.863. The model has R2 adjusted relative risk of 0.725. CONCLUSION: LDL-apheresis could be the first line treatment of isolated hyperLp(a)lipidemia when CAD is established. New CAD events/cardiac interventions were not observed.

[The Italian Registry for Therapeutic Apheresis: fifteen years of activity]. / Il registro italiano di aferesi terapeutica: quindici anni di attivita'

There is currently no consensus about the indications for therapeutic apheresis, also due to the lack of large clinical trials. A registry where all the data can be organized and analyzed therefore becomes a priority for all professionals involved in apheresis. The Apheresis Study Group of the Italian Society of Nephrology has instituted a registry for data collection. This report describes data collected from 1994 to 2008 by 68 units of different specialties in 15 Italian regions. Data about 29,260 treatments on 2,503 patients were recorded. Plasma exchange accounted for 43.4% of the procedures; 37% of these were performed by filtration. Plasma treatment was used in 48% of procedures, in particular with protein A immunoadsorption (11%), LDL-cholesterol apheresis by dextran sulfate adsorption (13%), and semiselective cascade or double filtration (12.5%). Cell apheresis, limited to photopheresis and leukocytapheresis, was used in 3.6% of cases, and whole blood treatment, with different techniques, in 5% of cases for the treatment of dyslipidemia, liver failure and sepsis. These procedures account for about 20% of the estimated therapeutic apheresis performed in Italy according to the national survey performed for the year 2005 by the Italian Apheresis and Cell Manipulation Society. The data collected are sufficiently informative to show a definite trend to use plasma/whole blood treatments as often as possible. The registry not only is a tool for consultation and information, but also a platform to plan and realize interdisciplinary and multicenter clinical trials.

A paraneoplastic retroperitoneal fibrosis resistant to corticosteroids treated with tamoxifen.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by an inflammatory proliferative fibrosing process occurring in the retroperitoneum, often causing urinary tract obstruction. Medical therapy is not well-defined, but glucocorticoids have been the mainstay of therapy. Recently, positive response to tamoxifen, an antiestrogen drug, has been reported among patients with RPF. We report the case of a 65-year-old male with a renal cell carcinoma in the upper pole of the right kidney showing acute renal failure due to a biopsy-confirmed RPF determining bilateral hydronephrosis. After polar resection of the right kidney, a high-dose oral steroid therapy did not modify the hydronephrosis. At 6 months, therapy with tamoxifen determined the retroperitoneal fibrotic mass regression and resolved the ureteral obstruction, that persists at the 13th month of follow-up. Tamoxifen can be considered as an effective alternative to corticosteroids and immunosuppressors in treating RPF.