Bosentan Does Not Affect Renal Resistive Index in Scleroderma/Systemic Sclerosis Patients.

INTRODUCTION: If properly evaluated, chronic kidney disease can be found in up to 50% of patients with systemic sclerosis (SSc). The renal resistive index (RRI) is a marker of intrarenal vascular resistance and can predict SSc-associated vasculopathy. This study aimed to determine the impact of bosentan, a nonselective endothelin-1 receptor antagonist, on RRI and kidney function in SSc patients with recurrent digital ulcers. METHODS: Twenty-one patients (age 57 ± 9 years, 19 females) were recruited in a 16-week prospective open-label uncontrolled study. Standardized procedures were used to measure general clinical and laboratory characteristics, systolic, diastolic, and mean arterial pressure (MAP), pulse pressure (PP), diastolic to systolic blood pressure (D/S) ratio, and urinary endothelin-1 levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate kidney function as an estimated glomerular filtration rate (eGFR). RRI was measured by Doppler ultrasound as the average of three samplings of intrarenal blood flow in different kidney regions of both kidneys. Patients with secondary causes of kidney disease or kidney diseases associated with albuminuria were excluded. RESULTS: Bosentan treatment for 16 weeks did not change RRI (0.731 ± 0.049-0.730 ± 0.054, p = 0.925), but increased urine endothelin-1 to creatinine ratio (0.27 ± 0.15-0.49 ± 0.57 pg/mg, p = 0.032) and reduced MAP (123 ± 10-101 ± 11 mm Hg, p < 0.001), PP (76 ± 11-68 ± 10 mm Hg, p = 0.003), D/S ratio (0.563 ± 0.044-0.538 ± 0.031, p = 0.006), and eGFR (92 ± 20-84 ± 24 mL/min/1.73 m2, p = 0.003). DISCUSSION/CONCLUSION: In conclusion, in patients with SSc complicated by digital ulcers and normal to mildly diminished kidney function, bosentan had no effect on intrarenal hemodynamics, but reduced blood pressure levels and kidney function.

Elevated Intrarenal Resistive Index Predicted Faster Renal Function Decline and Long-Term Mortality in Non-Proteinuric Chronic Kidney Disease.

Background. Intrarenal resistive index (RI) ≥ 0.80 predicts renal outcomes in proteinuric chronic kidney disease (CKD). However, this evidence in non-proteinuric patients with CKD of unknown etiology is lacking. In this study, we assessed the effect of intrarenal RI on renal function and all-cause mortality in non-proteinuric patients with CKD of unknown etiology despite an extensive diagnostic work-up. Methods. Non-proteinuric CKD patients were evaluated in a retrospective longitudinal study. Progression of renal disease was investigated by checking serum creatinine levels at 1, 3, and 5 years and defined by a creatinine level increase of at least 0.5 mg/dL. The discrimination performance of intrarenal RI in predicting the 5-year progression of renal disease was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Results. One-hundred-thirty-one patients (76 ± 9 years, 56% males) were included. The median follow-up was 7.5 years (interquartile range 4.3−10.5) with a cumulative mortality of 53%, and 5-year renal disease progression occurred in 25%. Patients with intrarenal RI ≥ 0.80 had a faster increase of serum creatinine levels compared to those with RI < 0.80 (+0.06 mg/dL each year, 95% CI 0.02−0.10, p < 0.010). Each 0.1-unit increment of intrarenal RI was an independent determinant of 5-year renal disease progression (odds ratio 4.13, 95% CI 1.45−12.9, p = 0.010) and predictor of mortality (hazards ratio 1.80, 95% CI 1.05−3.09, p = 0.034). AUROCs of intrarenal RI for predicting 5-year renal disease progression and mortality were 0.66 (95% CI 0.57−0.76) and 0.67 (95% CI 0.58−0.74), respectively. Conclusions. In non-proteinuric patients with CKD of unknown etiology, increased intrarenal RI predicted both a faster decline in renal function and higher long-term mortality, but as a single marker, it showed poor discrimination performance.

Gene Polymorphism in Five Target Genes of Immunosuppressive Therapy and Risk of Development of Preeclampsia.

Pregnancy can be considered as an allogeneic transplant and preeclampsia can be seen as a failure of the acceptance mechanisms of this transplant as occurs in acute organ transplant rejection. Some genetic polymorphisms may be involved in its pathogenesis. Since the kidney is one of the organs mainly involved in preeclampsia, our study attempted to determine the frequencies of single nucleotide polymorphisms of DNA (SNP) in 3 genes (adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1)/multi drug reactivity 1 (MDR1) gene, interleukin 10 gene and tumor necrosis factor α gene) which are targets of immunosuppressive therapies and related to acute renal rejection. The study was an observational, monocentric, case-control study. We enrolled 20 women with severe preeclampsia and 10 women age-matched with regular pregnancy. Continuous variables were compared by the Student's t-test for independent variables or using the Mann-Whitney test depending on their distribution. We used Fisher test to compare categorical variables between cases and controls, while we used logistic regression model to evaluate which risk factor was associated with preeclampsia. Although there was no statistically significant difference between the two groups, we found different percentages of two of the polymorphisms considered (rs1045642 and rs2032582 in the gene ABCB1). Despite these results, our work may be helpful for future research to better understand the pathogenesis of preeclampsia.

Secondary hyperparathyroidism is associated with postpartum blood pressure in preeclamptic women and normal pregnancies.

BACKGROUND: Preeclampsia has been associated with features of secondary hyperparathyroidism. In this study, we examine the relationships of calcium metabolism with blood pressure (BP) in preeclamptic women and in a control group of normal (NORM) pregnancies in the postpartum. METHODS: Sixty-three consecutive preeclamptic women (age 35 ±â€Š6 years) were studied 4 weeks after delivery. We collected clinical and lab information on pregnancy and neonates and measured plasma and urinary calcium and phosphate, plasma parathyroid hormone (PTH) and 25-hydroxy vitamin D [25(OH)D], and performed 24-h ambulatory BP monitoring. BP and calcium metabolism of 51 preeclamptic were compared with 17 NORM pregnant women that matched for age, race, and postpartum BMI. RESULTS: 25(OH)D deficiency (<10 ng/ml) was found in 3% of preeclamptic women, insufficiency (10-30 ng/ml) in 67%, and NORM values (31-100 ng/ml) in the remaining 30%. Elevated plasma PTH (≥79 pg/ml) was found in 24% of preeclamptic women who had 25(OH)D plasma levels of 21.4 ±â€Š8.3 ng/ml. In these women, PTH levels was independently associated with 24-h SBP and DBP and daytime and night-time DBP. Prevalence of nondippers and reverse dippers was elevated (75% and 33%, respectively). No associations between calcium metabolism and neonates' characteristics of preeclamptic women were observed. Prevalence of vitamin D deficiency and insufficiency and of elevated plasma PTH levels were comparable in matched groups. Considering preeclamptic women and matched controls as a whole group, office SBP and DBP levels were associated with PTH independently of preeclampsia and other confounders. CONCLUSION: Features of secondary hyperparathyroidism are common in the postpartum. Preeclampsia and increased PTH levels were both independent factors associated with increased BP after delivery, and both might affect the future cardiovascular risk of these women.

Acute rejection in kidney transplantation and the evaluation of associated polymorphisms (SNPs): the importance of sample size.

Background Acute rejection (AR) is one of the most frequent complications after kidney transplantation (KT). Scientific evidence reports that some single-nucleotide polymorphisms (SNPs) located in genes involved in the immune response and in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs are associated with rejection in renal transplant patients. The aim of this study was to evaluate some SNPs located in six genes: interleukin-10 (IL-10), tumor necrosis factor (TNF), adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), uridine diphosphate glucuronosyltransferase family 1 member A9 (UGT1A9), inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2. Methods We enrolled cases with at least one AR after KT and two groups of controls: patients without any AR after KT and healthy blood donors. Genetic analysis on DNA was performed. The heterozygosity (HET) was determined and the Hardy-Weinberg equilibrium (HWE) test was performed for each SNP. The sample size was calculated using the QUANTO program and the genetic associations were calculated using the SAS program (SAS Institute Inc., Cary, NC, USA). Results In our previous preliminary study (sample size was not reached for cases), the results showed that patients with the C allele in the SNP rs1045642 and the A allele in the SNP rs2032582 of the ABCB1 gene had more frequent AR. In contrast, with the achievement of sample size, the trend of the previous data was not confirmed. Conclusions Our study highlights a fundamental aspect of scientific research that is generally presumed, i.e. the sample size of groups enrolled for a scientific study. We believe that our study will make a significant contribution to the scientific community in the discussion of the importance of the analysis and the achievement of sample size to evaluate the associations between SNPs and the studied event.

Mathematical rationalization for the renal tubular transport: revised concepts.

The current emphasis on kinetics and in situ control of molecular exchanges, across the tubular membrane, has not been paralleled by corresponding improvements in our understanding of tubular behaviour at the macroscopic level of classical physiology. In this paper, we propose a mathematical rationalization of macroscopic tubular transport by means of a principal transport equation, originating from the law of mass action between substrate and carrier. The other equations, derived from the main one, demonstrate the possibility of distinguishing between transporters with low affinity and high capacity and transporters with high affinity and low capacity. Moreover, our model formalizes both tubular reabsorption and tubular secretion. Regarding the renal calcium handling, our model confirms the two-compartment system proposed by Mioni in 1971, with some important variants, which are in agreement with the fractional reabsorptions of this cation along the tubule, as verified by micro-puncture technique. To obtain the frequency distribution of saturated tubules, we have utilized the infinitesimal analysis method, starting from the equations proposed by Smith in 1943, concluding that all titration curves result from the combined effect of enzymatic approach and anatomical heterogeneity of the nephrons. The theoretical equations included in our manuscript reflect substantial and palpable physiological mechanisms able to suggest diagnosis and therapy of some electrolyte and hormonal disorders. At the end of this paper, we highlight advantages and disadvantages detectable by comparing our mathematical approach with Marshall's and Bijvoet's methods, proposed, respectively, in 1976 and 1984.

Restless legs syndrome in dialysis patients: a comparison between hemodialysis and continuous ambulatory peritoneal dialysis.

Restless legs syndrome (RLS) is common in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). A few studies so far have investigated RLS prevalence in ESRD patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The aim of this study was to compare the prevalence, characteristics, consequences and predictors of RLS between HD and CAPD patients. We recruited 58 HD and 28 CAPD patients. A neurologist expert in sleep medicine performed RLS diagnosis during a face-to-face interview. The prevalence of RLS was slightly higher in HD than in CAPD patients (19 vs. 10.7%). RLS appeared after the onset of kidney complaint in HD patients; in contrast, in CAPD patients RLS preceded the occurrence of renal disease. Five HD patients reported that RLS symptoms occurred throughout the dialysis session. HD patients with RLS(+) had a higher mean number of HD sessions per week and a longer mean duration of HD session than the RLS(-) ones. Prevalence of females was significantly higher in CAPD patients with RLS(+) than in the RLS(-) ones. RLS frequently affects both HD and CAPD patients. RLS impaired sleep in both groups, but use of dopaminergic agents was uncommon in our sample. Dialysis schedule was associated with RLS in HD patients, while female sex was related to RLS in CAPD patients. Awareness concerning RLS identification and treatment in HD and CAPD patients is recommended.

Effects of exercise in renal transplant recipients.

Even after a successful renal transplantation, the renal transplant recipients (RTRs) keeps on suffering the consequences of the uremic sickness. Cardiovascular risk, work capacity, and quality of life do not improve according to expectations since biological and psychological problems are not completely solved by pharmacological treatment. Furthermore, post-transplant treatment, per se, induces additional problems (i.e., side effects of drugs). It becomes, indeed, very important to insert "non-pharmacological" therapies able to reverse this trend. Exercise may represent an important contribution in the solution of this problem. In fact, many studies have demonstrated, in the last two decades, that physical training is able both, to improve graft function, work capacity and quality of life, and to reduce cardiovascular risk. In conclusion, if the analysis of the available data suggests that an appropriate dose of physical training represent a useful, safe and non-pharmacologic contribution to RTR treatment, it becomes a kidney transplantologist responsibility to introduce exercise in the current therapy of RTRs.

A case-control study on restless legs syndrome in nondialyzed patients with chronic renal failure.

Restless legs syndrome (RLS) is a possible consequence of end-stage renal disease. However, conclusive data on the association between RLS and chronic renal failure (CRF) in nondialyzed patients are still lacking. The aims of this study were: (1) to look for an association between RLS and CRF in nondialyzed patients; (2) to analyze the characteristics of RLS and its consequences on nocturnal rest in nondialyzed patients with CRF; (3) to identify possible predictors of RLS occurrence in nondialyzed patients with CRF. We recruited 138 nondialyzed patients with CRF (mean age: 69.8 +/- 11.7 years; male: 61.6%) and 151 controls (mean age: 60.2 +/- 18.6 years; male: 42.4%). An expert in sleep medicine investigated the presence of RLS by means of a face-to-face interview. Fifteen nondialyzed CRF patients and five controls were diagnosed as RLS affected. A multivariate analysis confirmed that RLS was independently associated with CRF in nondialyzed patients (P = 0.004). CRF patients RLS(+) were more commonly women and showed the presence of an iron deficiency compared with the RLS(-) ones. Independent predictors of RLS in nondialyzed CRF patients were: female sex (OR: 10.7, 95% CI: 2.2-31.3; P = 0.004) and percentage of transferrin saturation (OR: 0.6, 95% CI: 0.4-0.9; P = 0.04). This is the first case-control study able to recognize an association between RLS and CRF in patients not yet on dialysis. Nephrologists should investigate and treat RLS in their nondialyzed patients with CRF. In particular, physicians should carefully investigate women and patients with iron deficiency in the presence of RLS symptoms.

Hepatocyte growth factor and transforming growth factor beta1 ratio at baseline can predict early response to cyclophosphamide in systemic lupus erythematosus nephritis.

OBJECTIVE: To determine whether the ratio of hepatocyte growth factor (HGF) to transforming growth factor beta1 (TGFbeta1) in systemic lupus erythematosus (SLE) nephritis could be a prognostic factor for response to therapy with cyclophosphamide (CYC) and steroids at 6 months, and to examine whether the molecular ratio of HGF to TGFbeta1 correlates with the activity index (AI) and chronicity index (CI) and has predictive value for remission at the sixth month. METHODS: Thirty-six SLE patients with new-onset nephritis, 25 of whom were treated with CYC and steroids, entered into a prospective observational cohort trial at a tertiary university referral center. Renal biopsy findings and clinical parameters were recorded for all patients. Histopathologic, clinical, and immunohistochemical data at baseline served to define the predictive value for the outcome at 6 months. RESULTS: AI and CI at baseline did not distinguish patients who had achieved remission from those who had not achieved remission after receiving CYC plus steroids. HGF and TGFbeta1 were expressed in the tubuli, not in the glomeruli. The CI correlated directly with the TGFbeta1 extension score (TGFbeta1-ES) (r = 0.43, P = 0.008), but correlated indirectly with the HGF intensity score (HGF-IS) (r = -0.39, P = 0.02) and the HGF-ES (r = -0.45, P = 0.006). An HGF-ES:TGFbeta1-ES ratio of >or=1 at baseline distinguished patients who had achieved remission from those who had not achieved remission, with a predictive value of 94%. CONCLUSION: These findings indicate that baseline expression of renal HGF and TGFbeta1 predicts short-term renal outcome after therapy with CYC and steroids.