Aortic Stiffness of Kidney Transplant Recipients Correlates with Donor Age

Increased aortic stiffness is a major factor responsible for the high cardiovascular mortality in patients with end-stage renal disease, but the impact of kidney transplantation on recipient aortic stiffness remains poorly defined. The use of expanded-criteria kidney donors is associated with decreased recipient survival compared with the use of standard-criteria donors, although the underlying mechanisms are incompletely understood. It was hypothesized that donor characteristics may affect recipient aortic stiffness, which may contribute to cardiovascular mortality in these patients. Aortic stiffness was evaluated by measurement of carotid-femoral pulse wave velocity in 74 cadaveric kidney recipients at 3 and 12 mo after transplantation. At 3 mo, aortic stiffness was associated exclusively with recipient-related factors: Age, gender, and mean BP. At 12 mo, age of the donor kidney emerged as an additional determinant. The change in aortic stiffness between 3 and 12 mo strongly correlated with donor age; stiffness improved in recipients of young kidneys (first tertile of donor age) and worsened in recipients of older kidneys (upper tertile of donor age). At 12 mo, the carotid-femoral pulse wave velocity was >1 m/s higher in recipients of the oldest kidneys than in the recipients of younger kidneys. The association between donor age and aortic stiffness was independent of recipient age, gender, mean BP, pretransplantation dialysis duration, conventional cardiovascular risk factors, medication, posttransplantation events, and GFR. These results demonstrate that the impact of kidney transplantation on recipient aortic stiffness is dependent on donor age and suggest that ongoing damage to large arteries might contribute to the mechanism underlying the association of old-donor kidneys and increased cardiovascular mortality

Imported Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis

International audienc

Rare Variants in Complement Gene in C3 Glomerulopathy and Immunoglobulin-Mediated Membranoproliferative GN

International audienceBackground C3 glomerulopathy and idiopathic immunoglobulin-mediated membranoproliferative GN (Ig-MPGN) are rare complement-mediated kidney diseases. Inherited forms of C3 glomerulopathy/Ig-MPGN are rarely described. Methods Three hundred ninety-eight patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102) from a national registry were screened for three complement genes: factor H ( CFH ), factor I ( CFI ), and C3 . Patients with rare variant (minor allele frequency <0.1%) were included. Epidemiologic, clinical, and immunologic data at diagnosis and kidney outcomes of patients were retrospectively collected. Results Fifty-three different rare variants, including 30 (57%), 13 (24%), and ten (19%) in CFH , CFI , and C3 variants, were identified in 66/398 (17%) patients. Thirty-eight (72%) variants were classified as pathogenic, including 20/30 (66%) and 11/13 (84%) variants in CFH and CFI , respectively, impairing synthesis of factor H or factor I regulators. Fifteen of 53 (27%) variants were of unknown significance. At diagnosis, 69% of patients were adult (median age of 31 years). With the exception of biologic stigma of thrombotic microangiopathy, which was more frequent in patients with CFI variants (5/14 [36%] versus 1/37 [3%] and 0% in the CFH group and C3 group, respectively, P < 0.001), the clinical and histologic features were similar among the three variants groups. The kidney outcome was poor regardless of the age at onset and treatment received. Sixty-five percent (43/66) of patients with rare variant reach kidney failure after a median delay of 41 (19–104) months, compared with 28% (55/195) after a median delay of 34 (12–143) months in the nonvariant group. Among 36 patients who received a kidney transplant, 2-year recurrence was frequent, occurring in 39% (12/31), without difference between variant groups, and led to graft failure in three cases. Conclusions In our cohort, 17% of C3 glomerulopathy/Ig-MPGN cases were associated with rare variants in the CFH , CFI , or C3 genes. In most cases, a quantitative deficiency in factor H or factor I was identified. The presence of a rare variant was associated with poor kidney survival. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000252.mp