Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.

BACKGROUND: Kidney transplantation (KT) may restore fertility in CKD. The reasons why materno-foetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling.Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of non-transplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. METHODS: We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD and 1418 low-risk controls recruited in 2 large Italian Units, in the same period (2000-2014). The following outcomes were considered: maternal and foetal death; malformations; preterm delivery; small for gestational age baby (SGA); need for the neonatal intensive care unit (NICU); doubling of serum creatinine or increase in CKD stage. Data were analysed according to kidney diseases, renal function (staging according to CKD-EPI), hypertension, maternal age, partity, ethnicity. RESULTS: Materno-foetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. KT patients with e-GFR >90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases ('progressive CKD') are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 versus 1: RR 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. CONCLUSIONS: The materno-foetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney diseas

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation

Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity

KIR gene frequencies and KIR haplotypes in patients and 221 healthy controls.

<p>KIR gene frequencies and KIR haplotypes in patients and 221 healthy controls.</p

Risk of chronic rejection according to the presence or absence of specific recipient (r) KIR and donor (d) HLA ligand combinations.

<p>Risk of chronic rejection according to the presence or absence of specific recipient (r) KIR and donor (d) HLA ligand combinations.</p

Glomerular filtration rate measured at 1, 6, 12, 24, 36, 48, 60 and 72 months after transplantation normalized to baseline levels measured at 1 month after transplantation.

<p>The error bar at each point represents the 95% Confidence Interval. The group of patients with low NK cell inhibition (completely lacking the two functional units rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a statistically significant difference in comparison to the groups of patients with either partial or high NK cell inhibition; P = 3.5·10⁻¹⁴ obtained by calculating the area under the curve.</p

Donor HLA KIR ligands and KIR-HLA ligand combinations in recipient/donor pairs.

<p>Donor HLA KIR ligands and KIR-HLA ligand combinations in recipient/donor pairs.</p

HLA Class I allele frequencies in cadaveric kidney donors and healthy controls.

<p>HLA Class I allele frequencies in cadaveric kidney donors and healthy controls.</p

KIR-HLA ligand mismatches/matches in the 174 recipient/donor pairs.

<p>KIR-HLA ligand mismatches/matches in the 174 recipient/donor pairs.</p