Federica Fassio

Pregnancy in CKD: whom should we follow and why?

BACKGROUND Chronic kidney disease (CKD) has a high prevalence in pregnancy. In a period of cost constraints, there is the need for identification of the risk pattern and for follow-up. METHODS Patients were staged according to K-DOQI guidelines. The analysis was prospective, January 2000-June 2011. Two hundred and forty-nine pregnancies were observed in 225 CKD patients; 176 singleton deliveries were recorded. The largest group encompasses stage 1 CKD patients, with normal renal function, in which 127 singleton deliveries were recorded. No hard outcomes occurred (death; dialysis); therefore, surrogate outcomes were analysed [caesarean section, prematurity, need for neonatal intensive care unit (NICU)]. Stage 1 patients were compared with normal controls (267 low-risk pregnancies followed in the same setting) and with patients with CKD stages 2-4 (49 singleton deliveries); two referral patterns were also analysed (known diagnoses; new diagnoses). RESULTS The risk for adverse pregnancy rises significantly in stage 1 CKD, when compared with controls: odds ratios were caesarean section 2.73 (1.72-4.33); preterm delivery 8.50 (4.11-17.57); NICU 16.10 (4.42-58.66). The risks rise in later stages. There is a high prevalence of new CKD diagnosis (overall: 38.6%; stage 1: 43.3%); no significant outcome difference was found across the referral patterns. Hypertension and proteinuria are confirmed as independent risk factors. CONCLUSIONS CKD is a risk factor in pregnancy; all patients should be followed within dedicated programmes from stage 1. There is need for dedicated interventions and educational programmes for maximizing the diagnostic and therapeutic potentials in early CKD stages.

Kidney biopsy in pregnancy: evidence for counselling? A systematic narrative review

Kidney diseases, which have a prevalence of 3% in women of childbearing age, are increasingly encountered in pregnancy. Glomerulonephritis may develop or flare up in pregnancy, and a differential diagnosis with pre‐eclampsia may be impossible on clinical grounds. Use of kidney biopsy is controversial, but a systematic review has not been carried out to date.

Association of Low-Protein Supplemented Diets with Fetal Growth in Pregnant Women with CKD

BACKGROUND AND OBJECTIVES Women affected by CKD increasingly choose to get pregnant. Experience with low-protein diets is limited. The aim of this study was to review results obtained from pregnant women with CKD on supplemented vegan-vegetarian low-protein diets. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a single-arm, open intervention study between 2000-2012 of a low-protein diet in pregnant patients with stages 3-5 CKD or severe proteinuria (>1 g/d in the first trimester or nephrotic at any time). Stages 3-5 CKD patients who were not on low-protein diets for clinical, psychologic, or logistic reasons served as controls. The setting was the Obstetrics-Nephrology Unit dedicated to kidney diseases in pregnancy. The treated group included 24 pregnancies--21 singleton deliveries, 1 twin pregnancy, 1 abortion, and 1 miscarriage. Additionally, there were 21 controls (16 singleton deliveries, 5 miscarriages). The diet was a vegan-vegetarian low-protein diet (0.6-0.8 g/kg per day) with keto-acid supplementation and 1-3 protein-unrestricted meals allowed per week. RESULTS Treated patients and controls were comparable at baseline for median age (35 versus 34 years), referral week (7 versus 8), eGFR (59 versus 54 ml/min), and hypertension (43.5% versus 33.3%); median proteinuria was higher in patients on the low-protein diet (1.96 [0.1-6.3] versus 0.3 [0.1-2.0] g/d; P<0.001). No significant differences were observed in singletons with regard to gestational week (34 versus 36) or Caesarean sections (76.2% versus 50%). Kidney function at delivery was not different, but proteinuria was higher in the diet group. Incidence of small for gestational age babies was significantly lower in the diet group (3/21) versus controls (7/16; chi-squared test; P=0.05). Throughout follow-up (6 months to 10 years), hospitalization rates and prevalence of children below the third percentile were similar in both groups. CONCLUSION Vegan-vegetarian supplemented low-protein diets in pregnant women with stages 3-5 CKD may reduce the likelihood of small for gestational age babies without detrimental effects on kidney function or proteinuria in the mother.

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.

Is renal hyperfiltration protective in chronic kidney disease-stage 1 pregnancies? A step forward unravelling the mystery of the effect of stage 1 chronic kidney disease on pregnancy outcomes

The correlation between advanced or proteinuric chronic kidney disease (CKD) and adverse pregnancy outcomes is intuitive, although how early CKD affects pregnancy remains unknown. Glomerular hyperfiltration is a physiological response to pregnancy, correlated with outcomes in hypertension or collagen diseases. The aim of the study was to correlate first trimester hyperfiltration with pregnancy outcomes in stage 1 CKD patients.

NEMO syndrome (incontinentia pigmenti) and systemic lupus erythematosus: A new disease association

Congenital diseases are increasingly being recognised in adults because of clinical mimicry, variable clinical picture or rarity of the disease; pregnancy is a valuable diagnostic occasion. The present case is the first report of an association report between NEMO syndrome (an acronym of the mutated, non-functioning gene, NF-kB essential modulator), a rare X-linked disease, characterised by developmental anomalies, immunodepression and skin lesions, and systemic lupus erythematosus (SLE). A 35-year-old patient affected by SLE sought clinical advice in the 8th week of gestation. The diagnosis of SLE dated back to the age of 24, when multisystemic manifestations (pleuropericarditis, weight loss, alopecia, skin involvement, joint pain, kidney involvement) were observed. She had been treated with steroids since 1999; immunosuppressive drugs had been added for short periods. Developmental anomalies werepresent, including oligodontia, retinal problems, anomalies of the corpus callosum and pes planovalgus. Family history included multiple miscarriages, dental malformations and oligodontia and skin blistering in the first months of life. On these bases, incontinentia pigmenti (IP; or NEMO syndrome) was diagnosed and confirmed by genetic testing. The NEMO gene is implicated in immune deficiencies as well as in autoimmune diseases. This report may suggest a role for NF-kB essential modulator in the pathogenesis of SLE, in the context of thecomplex immunologic deficiencies increasingly associated with autoimmune diseases.

Pregnancy, Proteinuria, Plant-Based Supplemented Diets and Focal Segmental Glomerulosclerosis: A Report on Three Cases and Critical Appraisal of the Literature

Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE–angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furthermore, proteinuria usually increases as an effect of therapeutic changes and pregnancy-induced hyperfiltration. Based on a favourable effect of low-protein diets on proteinuria and advanced CKD, our group developed a moderately protein-restricted vegan-vegetarian diet tsupplemented with ketoacids and aminoacids for pregnant patients. This report describes the results obtained in three pregnant patients with normal renal function, nephrotic or sub-nephrotic proteinuria, and biopsy proven diagnosis of focal segmental glomerulosclerosis, a renal lesion in which hyperfiltration is considered of pivotal importance (case 1: GFR (glomerular filtration rate): 103 mL/min; proteinuria 2.1 g/day; albumin 3.2 g/dL; case 2: GFR 86 mL/min, proteinuria 3.03 g/day, albumin 3.4 g/dL; case 3: GFR 142 mL/min, proteinuria 6.3 g/day, albumin 3.23 g/dL). The moderately restricted diet allowed a stabilisation of proteinuria in two cases and a decrease in one. No significant changes in serum creatinine and serum albumin were observed. The three babies were born at term (38 weeks + 3 days, female, weight 3180 g-62th centile; 38 weeks + 2 days, female, weight 3300 g-75th centile; male, 38 weeks + 1 day; 2770 g-8th centile), thus reassuring us of the safety of the diet. In summary, based on these three cases studies and a review of the literature, we suggest that a moderately protein-restricted, supplemented, plant-based diet might contribute to controlling proteinuria in pregnant CKD women with focal segmental glomerulosclerosis. However further studies are warranted to confirm the potential value of such a treatment strategy.

Reflux nephropathy and the risk of preeclampsia and of other adverse pregnancy-related outcomes: a systematic review and meta-analysis of case series and reports in the new millennium

BackgroundReflux nephropathy is a common urinary tract malformation, and a substantial cause of morbidity in women of childbearing age. While recent studies provide further new information on pregnancy-related outcomes, their results are heterogeneous and a systematic meta-analysis may help the interpretation. The aim of this review was to analyze pregnancy-related outcomes in the recent literature on reflux nephropathy (2000–2016), to perfect the estimation of risks, and to identify specific research needs.MethodsWe searched Medline, EMBASE and the Cochrane review databases for the period 2000–2016 (PROSPERO registration no. 42016042713). Selection criteria: all case series and case reports dealing with reflux nephropathy and reporting on at least one pregnancy outcome. Data were extracted from eligible case series (≥ 6 cases). For the outcomes preeclampsia (PE), pregnancy-induced hypertension (PIH), preterm birth, and newborns small for gestational age, we employed as a control group the low-risk pregnancies from a multicenter database including 1418 live-born singletons. Case reports were analyzed narratively.ResultsThe search retrieved 2507 papers, of which 7 case series and 4 case reports were retained. The series report on 434 women with 879 pregnancies; no study reported controls. Compared to the low-risk controls, the meta-analysis showed an increased risk of PIH (odds ratio, OR 5.55; confidence interval, CI 3.56–8.66), PE (OR 6.04; CI 2.41–15.13), and all hypertensive disorders combined (OR 10.43; CI 6.90–15.75). No difference was observed in preterm delivery and caesarean sections. A higher incidence of stillbirth was reported in one paper. Conversely, the 4 case reports (on 10 pregnancies) alert us to a potentially severe complication, hydro(uretero)nephrosis with or without infection.ConclusionReflux nephropathy is associated with an increased risk of PIH and PE, but not of preterm delivery, suggesting the occurrence of late ‘maternal’ PE. The finding of a higher incidence of stillbirths in one series requires further analysis. Strict follow-up of these women is needed, in particular in late pregnancy stages, to avoid and manage in particular hypertensive pregnancy complications.

A Systematic Review on Materno-Foetal Outcomes in Pregnant Women with IgA Nephropathy: A Case of “Late-Maternal” Preeclampsia?

Background: IgA nephropathy is the most common primary glomerulonephritis in pregnancy and shares with other immunologic diseases and kidney diseases a relationship with adverse maternal outcomes, whose entity and pattern is only partially quantified. Recent studies provide new information and a systematic review regarded progression of kidney disease. The discussion of the outcomes with respect to low-risk pregnancies may help to perfect the estimation of the risks, and to identify specific research needs. Methods: A search strategy was built on Medline, EMBASE and the Cochrane review for the period January 2000–April 2017, aimed at retrieving both case series (defined as with at least 6 pregnancies in women with IgA nephropathy) and case reports, to look into rare occurrences. All papers, with or without control groups, were selected if they reported on at least one pregnancy outcome, or on long-term kidney function. Search strategy, paper selection and data extraction were done in duplicate (PROSPERO N 42016042623). Meta-analysis of case series was performed with Metanalyst Beta 3.13. Case reports were analysed narratively. Results: The search retrieved 556 papers, of which 27 were included (13 series and 14 case-reports). The case series report on 581 women with 729 pregnancies. The analysis was performed in comparison to the available control groups: 562 non-pregnant controls were available for the analysis of progression of kidney disease. As for pregnancy related outcomes (preeclampsia (PE), pregnancy induced hypertension (PIH), preterm birth, small babies), we meta-analyzed the data with respect to the only series of low-risk pregnancies (1418 pregnancies). When compared with women who never got pregnant after diagnosis of IgA nephropathy, in the present meta-analysis pregnancy in women with IgA nephropathy was not associated with a higher risk of progression of kidney disease, possibly due to the overall preserved kidney function at baseline: end-stage kidney disease (OR 0.68; CI 0.28–1.65). Conversely, the incidence of adverse pregnancy-related outcomes was increased compared to low-risk controls: PE and PIH were more than ten-fold increased (OR 11.80; CI 7.53–18.48 and OR 10.39; CI 5.45–19.80), while the increase in risk of preterm birth and “low birth weight babies” was less marked (OR 3.37; CI 1.91–5.95 and OR 2.36; CI 1.52–3.66), a discrepancy suggesting the occurrence of “late” or “maternal” PE, that may affect less severely foetal growth or shorten gestation. In conclusion, in the present meta-analysis IgA nephropathy was not associated with an increased progression of kidney disease. The more than ten-fold increased risk of PIH and PE, in combination with a doubled risk of small babies, suggests the occurrence of “late” or “maternal” PE, usually less affecting early foetal growth. This finding may be of help in defining control policies, while further research is needed to guide clinical management.

Simplified laparoscopic sacropexy avoiding deep vaginal dissection

To evaluate the safety and efficacy of a “simplified” laparoscopic sacropexy approach.