Any reduction in maternal kidney mass makes a difference during pregnancy in gestational and fetal outcome.

Little is known about the effect tubulointerstitial nephropathies have in modulating maternal-fetal outcomes in pregnancy. Therefore, we analyzed the main outcomes of pregnancy in these women to gain a better understanding of the role of a reduction in maternal kidney mass. From the Torino Cagliari Observational Study (TOCOS) cohort, we selected 529 patients with a diagnosis of tubulointerstitial disease and focused on 421 patients with chronic kidney disease (CKD) stage 1, without hypertension but with proteinuria less than 0.5 g/day at referral. From a cohort of 2969 singleton deliveries from low-risk pregnancies followed in the same settings we selected a propensity score matched control cohort of 842 pregnancies match 2:1 for age, parity, body mass index, ethnicity, and origin. Time to delivery was significantly shorter in the study cohort 38.0 (Quartile 1-Quartile 3: 37.0-39.0) versus 39.0 (Q1-Q3 38.0-40.0) weeks, with respect to controls. Incidence of delivery of less than 37 gestational weeks significantly increased from controls (7.4%) to women with previous acute pyelonephritis (10.8%), other tubulointerstitial diseases (9.7%) and was the highest in patients with a single kidney (31.1%). Similarly, neonatal birthweight significantly and progressively decreased from controls (3260 g [Q1-Q3: 2980-3530]), previous acute pyelonephritis (3090 g [Q1-Q3: 2868-3405], other tubulointerstitial diseases (3110 g [Q1-Q3: 2840-3417]), and to solitary kidney (2910 g [Q1-Q3: 2480-3240]). Risk of developing preeclampsia was significantly higher in the CKD cohort (3.6% vs 1.7% in low-risk controls). Thus, even a small reduction in functional kidney mass, such as a pyelonephritic scar, is associated with a shorter duration of pregnancy and an increased risk of preterm delivery. The risk is proportional to the extent of parenchymal reduction and is highest in cases with a solitary kidney.

Pregnancy outcomes after kidney graft in Italy: are the changes over time the result of different therapies or of different policies? A nationwide survey (1978-2013).

BACKGROUND: Kidney transplantation is the treatment of choice to restore fertility to women on renal replacement therapy. Over time, immunosuppressive, support therapies and approaches towards high-risk pregnancies have changed. The aim of this study was to analyse maternal-foetal outcomes in two cohorts of transplanted women who delivered a live-born baby in Italy in 1978-2013, dichotomized into delivery before and after January 2000. METHODS: A survey involving all the Italian transplant centres was carried out, gathering data on all pregnancies recorded since the start of activity at each centre; the estimated nationwide coverage was 75%. Data on cause of ESRD, dialysis, living/cadaveric transplantation, drug therapy, comorbidity, and the main maternal-foetal outcomes were recorded and reviewed. Data were compared with a low-risk cohort of pregnancies from two large Italian centres (2000-14; Torino and Cagliari Observational Study cohort). RESULTS: The database consists of 222 pregnancies with live-born babies after transplantation (83 before 2000 and 139 in 2000-13; 68 and 121 with baseline and birth data, respectively), and 1418 low-risk controls. The age of the patients significantly increased over time (1978-99: age 30.7 ± 3.7 versus 34.1 ± 3.7 in 2000-13; P < 0.001). Azathioprine, steroids and cyclosporine A were the main drugs employed in the first time period, while tacrolimus emerged in the second. The prevalence of early preterm babies increased from 13.4% in the first to 27.1% in the second period (P = 0.049), while late-preterm babies non-significantly decreased (38.8 versus 33.1%), thus leaving the prevalence of all preterm babies almost unchanged (52.2 and 60.2%; P = 0.372). Babies below the 5th percentile decreased over time (22.2 versus 9.6%; P = 0.036). In spite of high prematurity rates, no neonatal deaths occurred after 2000. The results in kidney transplant patients are significantly different from controls both considering all cases [preterm delivery: 57.3 versus 6.3%; early preterm: 22.2 versus 0.9%; small for gestational age (SGA): 14 versus 4.5%; P < 0.001] and considering only transplant patients with normal kidney function [preterm delivery: 35 versus 6.3%; early preterm: 10 versus 0.9%; SGA: 23.7 versus 4.5% (P < 0.001); risks increase across CKD stages]. Kidney function remained stable in most of the patients up to 6 months after delivery. Multiple regression analysis performed on the transplant cohort highlights a higher risk of preterm delivery in later CKD stages, an increase in preterm delivery and a decrease in SGA across periods. CONCLUSIONS: Pregnancy after transplantation has a higher risk of adverse outcomes compared with the general population. Over time, the incidence of SGA babies decreased while the incidence of 'early preterm' babies increased. Although acknowledging the differences in therapy (cyclosporine versus tacrolimus) and in maternal age (significantly increased), the decrease in SGA and the increase in prematurity may be explained by an obstetric policy favouring earlier delivery against the risk of foetal growth restriction.

Absence of IL-6 Receptor Blockade Effect on the Outcomes of Transplant Glomerulopathy in the Absence of Anti-HLA Donor-specific Antibodies.

Background: Transplant glomerulopathy (TG) is the hallmark of chronic antibody-mediated rejection but often occurs without anti-HLA donor-specific antibodies (DSAs) in the assumption that other DSAs may be the effectors of the tissue injury. Recently, we reported a positive effect of interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ) in TG/DSA+. In the present study, we investigate the effect of TCZ in a cohort of TG cases without detectable anti-HLA DSAs. Methods: Single-center retrospective analysis of TG cases without anti-HLA DSAs (TG/DSA) treated with TCZ for chronic antibody-mediated rejection as first-line therapy evaluated through clinical, protocol biopsies, and gene expression analyses was included. Results: Differently from TG/DSA+, TG/DSA- showed a progressive reduction in the estimated glomerular filtration rate at 12 mo and after that with no significant modification in microvascular inflammation or C4d+. No upregulation in tight junction protein-1, aldo-keto reductase family 1 member C3, and calcium/calmodulin-dependent serine protein kinase, documented in TG/DSA+, was noted in post-TCZ biopsies. The reduction of microvascular inflammation was associated with natural killer-cell reduction in TG/DSA+, whereas TG/DSA- tends to maintain or increase periglomerular/interstitial infiltration. Conclusions: In the absence of anti-HLA DSAs, TG behavior seems not to be modified by IL-6 receptor blockade. These results are at variance with observational studies and previous trials with IL-6 inhibitors in TG associated with anti-HLA DSAs. These data may fuel the hypothesis of different mechanisms underlying TGs (including the potentially different roles of natural killer cells) and suggest carefully selecting patients with TG for clinical trials or off-label treatment based on their antidonor serologic status.

[Onconephrology in Renal Transplant Patient: A Challenge for the Transplant Nephrologist].

Onconephrology, an emerging field in modern medicine, is gaining importance due to its intricate challenges derived from the mixing field of tumorous and renal diseases. The growing incidence of tumors in transplant patients requires preventive strategies and accurate monitoring. Pre-transplant screening is crucial, focusing on subjects with oncological history. Post-transplant follow-up must be personalized, tailoring screenings for patients with cancer history. Immunosuppressive therapy, although essential to prevent organ rejection, represents a delicate balance between controlling the immune response and cancer risk management. Immune checkpoint inhibitors emerge as a fascinating potential for cancer therapy, but their use in transplant patients requires caution and further research to carefully evaluate their safety and effectiveness, balancing potential benefits with actual risk of rejection. In summary, onconephrology is a growing field that requires an interdisciplinary approach and constant research, aimed at successfully addressing the complex challenges associated with oncological diseases in renal and transplant patients.

Bacterial and Viral Infection and Sepsis in Kidney Transplanted Patients.

Kidney transplanted patients are a unique population with intrinsic susceptibility to viral and bacterial infections, mainly (but not exclusively) due to continuous immunosuppression. In this setting, infectious episodes remain among the most important causes of death, with different risks according to the degree of immunosuppression, time after transplantation, type of infection, and patient conditions. Prevention, early diagnosis, and appropriate therapy are the goals of infective management, taking into account that some specific characteristics of transplanted patients may cause a delay (the absence of fever or inflammatory symptoms, the negativity of serological tests commonly adopted for the general population, or the atypical anatomical presentation depending on the surgical site and graft implantation). This review considers the recent available findings of the most common viral and bacterial infection in kidney transplanted patients and explores risk factors and outcomes in septic evolution.

Plant-Based Diets Improve Maternal-Fetal Outcomes in CKD Pregnancies.

Reducing protein intake in patients with chronic kidney disease (CKD) limits glomerular stress induced by hyperfiltration and can prevent the progression of kidney disease; data in pregnancy are limited. The aim of this study is to analyze the results obtained in CKD patients who followed a plant-based moderately protein-restricted diet during pregnancy in comparison with a propensity-score-matched cohort of CKD pregnancies on unrestricted diets. A total of 52 CKD pregnancies followed up with a protein-restricted plant-based diet (Torino, Italy) were matched with a propensity score based on kidney function and proteinuria with CKD pregnancies with unrestricted protein intake (Cagliari Italy). Outcomes included preterm (<37 weeks) and very preterm (<34 weeks) delivery and giving birth to a small-for-gestational-age baby. The median age in our cohort was 34 years, 63.46% of women were primiparous, and the median body mass index (BMI) was 23.15 kg/m2 with 13.46% of obese subjects. No statistical differences were found between women on a plant-based diet and women who were not in terms of age, parity, BMI, obesity, CKD stage, timing of referral, or cause of CKD. No differences were found between the two groups regarding the week of delivery. However, the combined negative outcome (birth before 37 completed gestational weeks or birth-weight centile <10) occurred less frequently in women following the diet than in women in the control group (61.54% versus 80.77%; p = 0.03). The lower risk was confirmed in a multivariable analysis adjusted for renal function and proteinuria (OR: 0.260 [Q1:0.093-Q3:0.724]; p = 0.010), in which the increase in proteinuria from the first to the last check-up before delivery was lower in patients on plant-based diets (median from 0.80 to 1.87 g/24 h; p: ns) than in controls (0.63 to 2.39 g/24 h p <0.0001). Plant-based, moderately protein-restricted diets in pregnancy in patients with CKD are associated with a lower risk of preterm delivery and small-for-gestational-age babies; the effect may be mediated by better stabilization of proteinuria.

Immunosuppression in pregnant women with renal disease: review of the latest evidence in the biologics era.

Care of pregnant woman, including fertility and procreation counseling, has become a significant part of the nephrological practice in the last years. In this context, the management of immunosuppression assumes a primary role both for autoimmune diseases and for post-transplant follow up. The present review analyzes the latest evidence on immunosuppressive drugs of current use in nephrology and kidney transplantation. Although the placenta inactivates prednisone and prednisolone, it is advisable to limit the dose to the minimal effective one, to prevent side effects. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancies in autoimmune diseases because of the safety profile and its steroid-sparing property. In lupus nephropathy, hydroxychloroquine is a current indication in the prevention of flares. Cyclosporine and tacrolimus can also be used as steroid-sparing agents as well as in post-transplant maintenance therapy. Experience on mammalian target of rapamycin inhibitors is limited and its use during pregnancy is still controversial even if initial positive data are emerging. Intravenous immunoglobulins are safe and represent an important option for relapses of lupus and vasculitis. Mycophenolate mofetil and cyclophosphamide are to avoid. An important part is reserved to biologic agents, which are having a huge impact on therapy protocols for several pathologies. Data on the utilization of these molecules during pregnancy, however, are still scant and therefore they do not yet allow a definitive evaluation of their safety profile.

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 chronic kidney disease (CKD). The reasons why maternofetal 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 nontransplanted 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 fetal death; malformations; preterm delivery; small for gestational age (SGA) baby; need for the neonatal intensive care unit; doubling of serum creatinine or increase in CKD stage. Data were analyzed according to kidney diseases, renal function (staging according to CKD-epidemiology collaboration), hypertension, maternal age, parity, ethnicity. RESULTS: Maternofetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. Kidney transplantation patients with estimated glomerular filtration rate greater than 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 vs 1: relative risk 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 maternofetal 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 disease.

Neutrophil Gelatinase Associated Lipocalin Is an Early and Accurate Biomarker of Graft Function and Tissue Regeneration in Kidney Transplantation from Extended Criteria Donors.

BACKGROUND: Delayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD. METHODS: We evaluated plasma levels of NGAL in 50 KT patients from ECD in the first 4 days after surgery or after Tac introduction. RESULTS: Plasma levels of NGAL at day 1 were significantly higher in DGF group. In the non DGF group, NGAL discriminated between slow or immediate graft function and decreased more rapidly than serum creatinine. NGAL increased after Tac introduction, suggesting a role as marker of drug toxicity. In vitro, hypoxia and Tac induced NGAL release from tubular epithelial cells (TEC) favoring an autocrine loop that sustains proliferation and inhibits apoptosis (decrease of caspases and Bax/Bcl-2 ratio). CONCLUSIONS: NGAL is an early and accurate biomarker of graft function in KT from ECD favoring TEC regeneration after ischemic and nephrotoxic injury.