A comprehensive genotype-phenotype interaction of different Toll-like receptor variations in a renal transplant cohort.

To date, the impact of the TLR (Toll-like receptor) system on early and late kidney transplantation outcome, such as ARE (acute rejection episodes) or cardiovascular morbidity and mortality, has still not been elucidated conclusively. Genetically determined alterations in TLR expression exhibit a possibility to evaluate their role in transplantation. In the present study, we sought to determine a comprehensive genotype-phenotype association with early and late allograft outcomes. We studied 11 SNPs (single nucleotide polymorphisms) in TLR2, TLR3, TLR4, TLR5, TLR9 and within a co-molecule CD14 in 265 patients receiving their first kidney transplant and the association of these with the occurrence of DGF (delayed graft function), ARE or MACE (major adverse cardiovascular events). ARE were significantly more frequent in patients carrying the TLR3 TT/CT allele (43.8 compared with 25.8%; P=0.001) as were rates of DGF (21.4 compared with 12.0%; P=0.030). Furthermore, TLR9 was significantly involved in the occurrence of MACE (TLR9 -1237; P=0.030). Interestingly, there was no significant effect of any TLR polymorphism on graft survival or renal function and the incidence of any infection, including CMV (cytomegalovirus) infection. In conclusion, our present study in renal transplant recipients suggests that the TLR system may be involved in both acute rejection and MACE. Modulation of the TLR system may be a promising target in future therapeutic strategies.

[A 58-year-old hypertensive patient with primary hyperaldosteronism and renal artery stenosis]. / 58-jähriger Patient mit primärem Hyperaldosteronismus und Nierenarterienstenose bei arterieller Hypertonie.

BACKGROUND: Secondary hypertension can rarely be caused by different disorders as shown in the present case with simultaneous occurrence of two possible causes. CASE REPORT: Magnetic resonance imaging findings of a 58-year-old patient showed an eccentric left renal artery stenosis of 60-70% and an inhomogeneous tumor of the left adrenal gland. After percutaneous transluminal angioplasty, elevated plasma aldosterone concentrations persisted. Adrenal vein sampling in the authors' hospital confirmed a primary hyperaldosteronism due to unilateral adenoma. Subsequently, unilateral laparoscopic adrenalectomy was performed. CONCLUSION: Atherosclerotic renal artery stenosis stimulates the renin-angiotensin system and thereby causes secondary hypertension. Furthermore, adrenal disorders that lead to abnormal aldosterone secretion, i.e., primary hyperaldosteronism, often result in secondary hypertension. Though the simultaneous occurrence of two potential causes of secondary hypertension is rare, it has to be considered for differential diagnosis and therapy. The presumed pathophysiological relevance should guide the order of therapeutic measures.

Is inflammation prior to renal transplantation predictive for cardiovascular and renal outcomes?

OBJECTIVES: Markers of non-specific inflammation, such as C-reactive protein (CRP) or leukocyte count are increased in end-stage renal disease patients. Recent studies have shown positive associations between inflammatory markers and cardiovascular mortality in kidney transplant recipients, but these analyses had been limited by sample size. The aim of our study was to determine the association between pretransplant CRP levels and leukocyte counts with posttransplant outcome in a prospectively enrolled cohort of kidney transplant recipients. METHODS: 459 consecutive patients transplanted from July 1995 to December 2007 were analyzed. Both markers were obtained prior to transplantation and patients were grouped according to baseline CRP levels (<5mg/l or >or=5mg/l) or leukocyte counts (<10,000/microl or >or=10,000/microl). RESULTS: Major cardiac events were associated with elevated pretransplant CRP levels (p<0.00003) but not leukocyte counts. Furthermore, more acute rejection episodes within 4 weeks or 6 months, as well as a lower probability of survival at 6 months were found in patients with elevated pretransplant CRP levels or leukocyte counts. CONCLUSION: Elevated pretransplant serum CRP level is a risk predictor for major cardiac events in renal transplant patients. It is also predictive, besides leukocyte counts, for acute rejection episodes. Elevated CRP levels and initial high leukocyte counts may prove to be useful markers for posttransplant course and warrant the close follow-up of such patients.