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Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study.

ABSTRACT: Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX.Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9-1.3) mg/dL, and 5.8 (5.4-7.6)] ?g/L, respectively), while urinary cGMP was reduced [270 (250-355) vs 581 (437-698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time.

SUBMITTER: Bellavia D

PROVIDER: S-EPMC4640880 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study.

Bellavia Diego D Cataliotti Alessandro A Clemenza Francesco F Baravoglia Cesar Hernandez CH Luca Angelo A Traina Marcello M Gridelli Bruno B Bertani Tullio T Burnett John C JC Scardulla Cesare C

PloS one 20151110 11

<h4>Background and aims</h4>Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX.<h4>Methods and results</h4>Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was inv ...[more]

PMID: 26556804

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Project description:Rationale & objectiveLive kidney donation is associated with a small increased risk for kidney disease and hypertension in African American donors. We investigated a possible association between donor family history of end-stage kidney disease (ESKD) and their postdonation kidney function and the development of hypertension. We tested whether this association was modified by kidney donation.Study designRetrospective cohort.Setting & participantsFormer African American live kidney donors between 1993 and 2010. Healthy nondonors were selected from the Coronary Artery Disease in Young Adults (CARDIA) Study.ExposureFamily history of ESKD in a first-degree relative.OutcomesKidney function and blood pressure ≥ 140/90 mm Hg or use of antihypertensive medications at follow-up.Analytical approachDonors were grouped based on family history of ESKD. Outcomes were first compared between donor groups and then between donors and healthy nondonors matched for demographics, follow-up time, and family history. A mixed-effect model was used to compare outcomes.ResultsOf 179 donors, 139 (78%) had a first degree relative with ESKD. Predonation characteristics were similar between the 2 groups. At a median follow-up of 11 years postdonation, there was no difference in postdonation estimated glomerular filtration rates (68 ± 19 vs 69 ± 13 mL/min/1.73 m2; P = 0.71) and the presence of albuminuria (P = 0.16). There was a trend toward a higher incidence of hypertension (51% vs 35%; P = 0.08) among donors with a family history of ESKD than for those without. Although there was no difference in annual change in estimated glomerular filtration rate (P = 0.17), the risk for hypertension was higher in donors than nondonors (relative risk, 2.44 [95% CI, 1.56-3.84]), but there was no interaction by family history (P = 0.11).LimitationsRetrospective small study. Lack of data across donor-recipient specific biological relationship.ConclusionsFamily history of ESKD is not associated with postdonation kidney function among African American kidney donors. Live kidney donation is associated with an increased risk for hypertension among African Americans, independent of donor family history of ESKD.

Project description:Background The myocardial cytoskeleton functions as the fundamental framework critical for organelle function, bioenergetics and myocardial remodeling. To date, impairment of the myocardial cytoskeleton occurring in the failing heart in patients with advanced chronic kidney disease has been largely undescribed. Methods and Results We conducted a 3-arm cross-sectional cohort study of explanted human heart tissues from patients who are dependent on hemodialysis (n=19), hypertension (n=10) with preserved renal function, and healthy controls (n=21). Left ventricular tissues were subjected to pathologic examination and next-generation RNA sequencing. Mechanistic and interference RNA studies utilizing in vitro human cardiac fibroblast models were performed. Left ventricular tissues from patients undergoing hemodialysis exhibited increased myocardial wall thickness and significantly greater fibrosis compared with hypertension patients (P<0.05) and control (P<0.01). Transcriptomic analysis revealed that the focal adhesion pathway was significantly enriched in hearts from patients undergoing hemodialysis. Hearts from patients undergoing hemodialysis exhibited dysregulated components of the focal adhesion pathway including reduced β-actin (P<0.01), β-tubulin (P<0.01), vimentin (P<0.05), and increased expression of vinculin (P<0.05) compared with controls. Cytoskeletal adaptations in hearts from the hemodialysis group were associated with impaired mitochondrial bioenergetics, including dysregulated mitochondrial dynamics and fusion, and loss of cell survival pathways. Mechanistic studies revealed that cytoskeletal changes can be driven by uremic and metabolic abnormalities of chronic kidney disease, in vitro. Furthermore, focal adhesion kinase silencing via interference RNA suppressed major cytoskeletal proteins synergistically with mineral stressors found in chronic kidney disease in vitro. Conclusions Myocardial failure in advanced chronic kidney disease is characterized by impairment of the cytoskeleton involving disruption of the focal adhesion pathway, mitochondrial failure, and loss of cell survival pathways.

Project description:Data regarding health outcomes among living kidney donors are lacking, especially among nonwhite persons.We linked identifiers from the Organ Procurement and Transplantation Network (OPTN) with administrative data of a private U.S. health insurer and performed a retrospective study of 4650 persons who had been living kidney donors from October 1987 through July 2007 and who had post-donation nephrectomy benefits with this insurer at some point from 2000 through 2007. We ascertained post-nephrectomy medical diagnoses and conditions requiring medical treatment from billing claims. Cox regression analyses with left and right censoring to account for observed periods of insurance benefits were used to estimate absolute prevalence and prevalence ratios for diagnoses after nephrectomy. We then compared prevalence patterns with those in the 2005-2006 National Health and Nutrition Examination Survey (NHANES) for the general population.Among the donors, 76.3% were white, 13.1% black, 8.2% Hispanic, and 2.4% another race or ethnic group. The median time from donation to the end of insurance benefits was 7.7 years. After kidney donation, black donors, as compared with white donors, had an increased risk of hypertension (adjusted hazard ratio, 1.52; 95% confidence interval [CI], 1.23 to 1.88), diabetes mellitus requiring drug therapy (adjusted hazard ratio, 2.31; 95% CI, 1.33 to 3.98), and chronic kidney disease (adjusted hazard ratio, 2.32; 95% CI, 1.48 to 3.62); findings were similar for Hispanic donors. The absolute prevalence of diabetes among all donors did not exceed that in the general population, but the prevalence of hypertension exceeded NHANES estimates in some subgroups. End-stage renal disease was identified in less than 1% of donors but was more common among black donors than among white donors.As in the general U.S. population, racial disparities in medical conditions occur among living kidney donors. Increased attention to health outcomes among demographically diverse kidney donors is needed. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)

Dataset Information

Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study.

Publications

Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study.

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