Thyroid hormones may directly affect the kidney and altered kidney function may also contribute to thyroid disorders. The renal manifestations of thyroid disorders are based on hemodynamic alterations or/and to direct effects of thyroid hormones. The renin-angiotensin system plays a crucial role in the cross-talk between the thyroid and the kidney. Hypothyroidism may be accompanied by an increase of serum creatinine and reduction of glomerular filtration rate (GFR), whereas hyperthyroidism may increase GFR. Treatment of thyroid disorders may lead to normalization of GFR. Primary and subclinical hypothyroidism and low triiodothyronine (T3) syndrome are common features in patients with chronic kidney disease (CKD). In addition low levels of thyroid hormones may predict a higher risk of cardiovascular and overall mortality in patients with end-stage renal disease. The causal nature of this correlation remains uncertain. In this review, special emphasis is given to the thyroid pathophysiology, its impact on kidney function and CKD and the interpretation of laboratorial findings of thyroid dysfunction in CKD.

The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation.

Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on-treatment platelet reactivity. J Thromb Haemost 2011; 9: 2379-85.Summary. Background: High on-treatment platelet reactivity (HTPR) is frequent in patients on hemodialysis (HD) receiving clopidrogel. Objectives: The primary aim of this study was to determine the antiplatelet effects of prasugrel vs. high-dose clopidogrel in patients on HD with HTPR. Patients/Methods: We performed a prospective, single-center, single-blind, investigator-initiated, randomized, crossover study to compare platelet inhibition by prasugrel 10 mg day 3), P < 0.001). The LS mean differences between the two treatments were ) 113.4 PRU (95% CI ) 152.9 to ) 73.8, P < 0.001) and ) 163.8 PRU (95% CI ) 218.1 to ) 109.2, P < 0.001) in non-carriers and carriers of at least one CYP2C19*2 allele, respectively. HTPR rates were lower for prasugrel than clopidogrel, in all patients (19% vs. 85.7%, P < 0.001) and in non-carriers (25.7% vs. 80%, P = 0.003). All carriers continued to show HTPR while receiving high-dose clopidogrel, but none showed it while receiving prasugrel. Conclusions: In HD patients exhibiting HTPR following standard clopidogrel treatment, prasugrel 10 mg day -1 is significantly more efficient than doubling the clopidogrel dosage in achieving adequate platelet inhibition. Neither effect seems to be influenced by carriage of the loss-offunction CYP2C19*2 allele.

Background/Aims: Recent studies indicate that regulatory T-cells (Tregs) promote transplant tolerance. We studied Treg levels in 39 stable renal transplant recipients to determine the sizes of the Treg populations and the effects of treatment regimens thereof. Methods: All patients (19 with good graft function and 20 with chronic allograft nephropathy) received induction therapy (basiliximab) and were on triple immunosuppressive regimens with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil (MMF) or everolimus and steroids. Twenty healthy subjects served as controls. Whole blood samples were stained with anti-CD4, CD25, CD127, and FoxP3 antibodies and analyzed by flow cytometry to determine CD4+CD25^highFoxP3± and CD4+ CD25^highCD127^–/low Treg levels. Results:All patients had significantly reduced CD4+CD25^highFoxP3± but no CD4+ CD25^highCD127^–/low Treg levels compared to controls. Renal allograft function did not correlate with Treg levels. Statistically significant correlations between CD4+CD25^highFoxp3+ Tregs and tacrolimus levels and CD4+CD25^highFoxp3– Tregs and HLA-DR mismatching were detected. Patients receiving MMF had significantly higher CD4+CD25^highFoxp3+ Tregs compared to patients on everolimus who were also receiving lower doses of calcineurin inhibitors. Conclusion:Overall, immunosuppression lowers CD4+CD25^highFoxP3± Treg levels significantly in the periphery in renal transplant recipients. In addition, different immunosuppressive regimens have different impacts on CD4+CD25^highFoxP3+ Tregs, a fact that may influence long-term allograft survival.

Testosterone deficiency and hypogonadism are common conditions in men with chronic kidney disease (CKD). A disturbed hypothalamic-pituitary-gonadal axis due to CKD is thought to contribute to androgen deficiency. Data from experimental studies support the hypothesis that exogenous administration of testosterone may induce the activation of the renin-angiotensin system (RAS), the production of endothelin and the regulation of anti- or/and proinflammatory cytokines involved in the pathogenesis of hypertension and kidney damage. On the other hand, low testosterone levels in male patients with CKD are paradoxically associated with a higher risk of morbidity and mortality, possibly explained by anemia, osteoporosis and cardiovascular disease. In this article, we present an overview of clinical and experimental studies of the impact of testosterone on the progression and prognosis of male patients with CKD; even today, this remains a controversial issue.