Association between serum resistin level and outcomes in kidney transplant recipients

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio‐demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition‐Inflammation in Transplant—Hungary Study (MINIT‐HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6‐year follow‐up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow‐up period (median [IQR]: 22[15–26] vs. 19[14–22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16–1.54) and 1.21(1.01–1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.     

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.     

Effect of tonsillectomy and its timing on renal outcomes in Caucasian IgA nephropathy patients

Purpose

The role of tonsillectomy in the treatment of IgA nephropathy in Caucasian patients is controversial.

Methods

A retrospective cohort study was conducted in 264 patients with biopsy-proven primary IgA nephropathy to examine the association between tonsillectomy and long-term renal survival, defined as the incidence of estimated glomerular filtration rates (eGFRs) of ≤30 ml/min/1.73 m² or end-stage renal disease (the composite of initiation of dialysis treatment or renal transplantation). The association of tonsillectomy with renal end-points was examined using the Kaplan–Meier method and Cox models.

Results

One-hundred and sixty-six patients did not undergo tonsillectomy (Group I, follow-up 130 ± 101 months) and 98 patients underwent tonsillectomy (Group II, follow-up 170 ± 124 months). The mean renal survival time was significantly longer for both end-points between those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Group I) (p < 0.001 and p = 0.005). The mean renal survival time was significantly longer for both end-points between those patients who had macrohaematuric episodes versus patients who had no macrohaematuric episodes (p = 0.035 and p = 0.019). Tonsillectomy, baseline eGFR and 24-h proteinuria were independent risk factors for both renal end-points.

Conclusion

Tonsillectomy may delay the progression of IgA nephropathy mainly in IgA nephropathy patients with macrohaematuria. Prospective investigation of the protective role of tonsillectomy in Caucasian patients is needed.     

Impact of Achieved Blood Pressures on Mortality Risk and End-Stage Renal Disease Among a Large,Diverse Hypertension Population

Background

Medical data or clinical guidelines have not adequately addressed the ideal blood pressure (BP) treatment targets for survival and renal outcome.

Objectives

This study sought to evaluate ranges of treated BP in a large hypertension population and compare risk of mortality and end-stage renal disease (ESRD).

Methods

A retrospective cohort study within the Kaiser Permanente Southern California health system was performed from January 1, 2006, to December 31, 2010. Treated hypertensive subjects ≥18 years of age were studied. Cox proportional hazards regression models were used to evaluate the risks (hazard ratios) for mortality and/or ESRD among different BP categories with and without stratification for diabetes mellitus and older age.

Results

Among 398,419 treated hypertensive subjects (30% with diabetes mellitus), mortality occurred in 25,182 (6.3%) and ESRD in 4,957 (1.2%). Adjusted hazard ratios (95% confidence intervals [CI]) for composite mortality/ESRD in systolic BP <110, 110 to 119, 120 to 129, 140 to 149, 150 to 159, 160 to 169, and ≥170 compared with 130 to 139 mm Hg were 4.1 (95% CI: 3.8 to 1.3), 1.8 (95% CI: 1.7 to 1.9), 1.1 (95% CI: 1.1 to 1.1), 1.4 (95% CI: 1.4 to 1.5), 2.3 (95% CI: 2.2 to 2.5), 3.3 (95% CI: 3.0 to 3.6), and 4.9 (95% CI: 4.4 to 5.5) respectively. Diastolic BP 60 to 79 mm Hg were associated with the lowest risk. The nadir systolic and diastolic BP for the lowest risk was 137 and 71 mm Hg, respectively. Stratified analyses revealed that the diabetes mellitus population had a similar hazard ratio curve but a lower nadir at 131 and 69 mm Hg but age ≥70 had a higher nadir (140 and 70 mm Hg).

Conclusions

Both higher and lower treated BP compared with 130 to 139 mm Hg systolic and 60 to 79 mm Hg diastolic ranges had worsened outcomes. Our study adds to the growing uncertainty about BP treatment targets.     

Restricting Kidney Transplant Wait‐Listing for Obese Patients: Let's Stop Defending the Indefensible

The allocation of limited medical resources represents an ethical dilemma that continues to generate lively debates. While the allocation of allografts to wait‐listed patients is done in a transparent manner, with its rules open to public debate and prone to continuous improvement, the practice of wait‐listing is not centrally regulated, and its rules are often less scrutinized. Denial of kidney transplant wait‐listing to obese individuals has been a common practice by most transplant centers. On the face of it, this practice is justified by commonly accepted ethical standards, yet there is now mounting evidence that these justifications do not withstand closer scrutiny. A candid and open debate in the Nephrology and Transplant community is needed to examine the true motivations that underlie the practice of denying wait‐listing to obese individuals, and to find a solution that is truly in the best interest of our patients.