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Special Issue "Kidney Diseases and Kidney Involvement in Pregnancy: the Crossroad of Obstetrics, Nephrology, Urology and Internal Medicine"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (5 February 2019)

Special Issue Editors

Guest Editor
Prof. Dr. Giorgina Barbara Piccoli

Nephrology, Centre Hospitalier Le Mans, Le Mans, France; Department of Clinical and Biological Sciences, ASOU San Luigi, University of Torino, 10043 Orbassano, Italy
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Interests: chronic kidney disease; dialysis; hemodialysis; nutritional aspects; Kidney disease and pregnancy; preeclampsia; glomerular diseases; polycystic kidney disease; history of medicine; bioethics aspects in chronic kidney disease; dialysis and transplantation
Guest Editor
Dr. Rossella Attini

Department of Surgery, University of Torino, Torino, Italy
E-Mail
Interests: obstetrics; pathological pregnancy; kidney disease in pregnancy; urological disease in pregnancy; cardiotocography; fetal monitoring in labour; STAN; operative delivery
Guest Editor
Dr. Gianfranca Cabiddu

Nephrology, Azienda Ospedaliera Brotzu, Cagliari, Italy
E-Mail
Interests: Clinical nephrology (in particular: pregnancy and kidney diseases; lupus and immunologic renal diseases; nutritional treatment of chronic kidney diseases and predialysis care; rare diseases); dialysis (and in particular peritoneal dialysis); epidemiology of chronic kidney disease and of its treatments

Special Issue Information

Dear Colleagues,

Obstetric Nephrology is a new branch of clinical nephrology gaining increasing attention in the last years.

There are at least four good reasons for this:

  • The great improvement in the care of high-risk pregnancy and in prenatal care.
  • The advances in Nephrology, in particular in dialysis care, making pregnancy, once almost impossible, a potential, albeit still difficult, option for women with end-stage kidney disease on dialysis.
  • The higher awareness of the importance of kidney involvement in different fields of internal medicine, such as diabetology, immunology or infectious diseases.
  • Patient empowerment, that puts the choice of having a baby more in the patient’s hands than in the physician’s ones, thus actually changing the balance in the case of “contraindicated” pregnancies.

Indeed, in 2018, the world kidney day fell in the same occasion of the international woman’s day, and this was the occasion for focussing the yearly campaign on women and kidney diseases in general and on pregnancy in kidney diseases in particular.

New knowledge suggests that even mild renal involvement, characterised by an initial reduction of functioning kidney tissue, without loss of kidney function, such as pyelonephritis scars, immunologic diseases or early diabetic nephropathy may increase pregnancy related risks.

Conversely, preeclampsia, HELLP syndrome and intrauterine growth restriction are associated with future risk of chronic kidney disease and hypertension in the mother and with an increased risk of cardiovascular, metabolic and kidney diseases in the babies, in particular if born small for gestational age or premature. The increasing age at pregnancy and the development of assisted fertilisation techniques may contribute to enhance the risk for preeclampsia; the impact on future kidney disease is a potential concern.

Due to the extreme heterogeneity of kidney diseases, as for pathogenesis, causes, stages and associated conditions we need more information on how to follow-up pregnancies in their presence; furthermore, the impact of the different combinations and grades of pre-term delivery, intrauterine growth restriction and neonatal problems on future health still needs being unravelled.

The present Special Issue aims to get new, multidisciplinary insights to improve knowledge and patient management.

Prof. Dr. Giorgina Barbara Piccoli
Dr. Rossella Attini
Dr. Gianfranca Cabiddu
Guest Editors

Manuscript Submission Information

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Keywords

  • Pregnancy
  • Kidney diseases
  • Preeclampsia
  • Small babies
  • Neonatal care
  • Dialysis
  • Kidney transplantation
  • Pyelonephritis
  • Immunologic diseases
  • Renal malformations
  • Diabetes and diabetic nephropathy
  • Hypertension
  • Obesity
  • Hypertensive disorders of pregnancy
  • Bioethics

Published Papers (15 papers)

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Editorial

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Open AccessEditorial
Kidney Diseases and Pregnancy: A Multidisciplinary Approach for Improving Care by Involving Nephrology, Obstetrics, Neonatology, Urology, Diabetology, Bioethics, and Internal Medicine
J. Clin. Med. 2018, 7(6), 135; https://doi.org/10.3390/jcm7060135
Received: 25 May 2018 / Accepted: 25 May 2018 / Published: 4 June 2018
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Abstract
This multidisciplinary series is aimed at offering readers many opportunities to appreciate how a clinical and ethical approach to pregnancy has changed in patients with kidney diseases and with related conditions, including diabetes, hypertension, and immunologic diseases. Furthermore, this series aims to focus [...] Read more.
This multidisciplinary series is aimed at offering readers many opportunities to appreciate how a clinical and ethical approach to pregnancy has changed in patients with kidney diseases and with related conditions, including diabetes, hypertension, and immunologic diseases. Furthermore, this series aims to focus on the fact that many issues remain unreslved, that there are enormous gaps in knowledge, and that the bioethical approach needs to integrated in the clinical practice, which would allow for a deeper appreciation of different cultural and religious backgrounds. Much still needs to be done to allow women suffering from all stages of chronic kidney disease (CKD) and those with predisposed conditions, so that they may experience safe pregnancies, starting from an increased awareness of the importance of CKD, even in its early stages, to the detection of risk factors. Women who have experienced preeclampsia or acute kidney injury in pregnancy need to have follow-up checks. The role of urinary infections, kidney stones, and urinary malformations is not fully acknowledged, nor have univocal control schedules and treatment schemas yet been defined for the different kidney diseases. In this regard, the fight for equitable treatment for all women with acute or chronic kidney disease in pregnancy and for the widespread prevention of adverse pregnancy-related and long-term outcomes is ultimately a battle for equitable healthcare. Full article
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Research

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Open AccessArticle
Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice
J. Clin. Med. 2019, 8(5), 663; https://doi.org/10.3390/jcm8050663
Received: 15 March 2019 / Revised: 30 April 2019 / Accepted: 8 May 2019 / Published: 11 May 2019
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Abstract
There is accumulating evidence for fetal programming of later kidney disease by maternal obesity or associated conditions. We performed a hypothesis-generating study to identify potentially underlying mechanisms. Female mice were randomly split in two groups and fed either a standard diet (SD) or [...] Read more.
There is accumulating evidence for fetal programming of later kidney disease by maternal obesity or associated conditions. We performed a hypothesis-generating study to identify potentially underlying mechanisms. Female mice were randomly split in two groups and fed either a standard diet (SD) or high fat diet (HFD) from weaning until mating and during pregnancy. Half of the dams from both groups were treated with metformin ((M), 380 mg/kg), resulting in four experimental groups (SD, SD-M, HFD, HFD-M). Caesarean section was performed on gestational day 18.5. Fetal kidney tissue was isolated from cryo-slices using laser microdissection methods and a proteomic screen was performed. For single proteins, a fold change ≥1.5 and q-value <0.05 were considered to be statistically significant. Interestingly, HFD versus SD had a larger effect on the proteome of fetal kidneys (56 proteins affected; interaction clusters shown for proteins concerning transcription/translation, mitochondrial processes, eicosanoid metabolism, H2S-synthesis and membrane remodeling) than metformin exposure in either SD (29 proteins affected; clusters shown for proteins involved in transcription/translation) or HFD (6 proteins affected; no cluster). By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet. Full article
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Open AccessArticle
Delayed Initiation of Hemodialysis in Pregnant Women with Chronic Kidney Disease: Logistical Problems Impact Clinical Outcomes. An Experience from an Emerging Country
J. Clin. Med. 2019, 8(4), 475; https://doi.org/10.3390/jcm8040475
Received: 12 February 2019 / Revised: 21 March 2019 / Accepted: 3 April 2019 / Published: 8 April 2019
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Abstract
Background: Chronic kidney disease (CKD) is associated with reduction of fertility and increased complications during pregnancy. The aim of this work is to analyze the clinical outcomes and risk factors in pregnant women who needed to start dialysis with different schedules in a [...] Read more.
Background: Chronic kidney disease (CKD) is associated with reduction of fertility and increased complications during pregnancy. The aim of this work is to analyze the clinical outcomes and risk factors in pregnant women who needed to start dialysis with different schedules in a public hospital in Mexico City, with particular attention on the interference of social and cultural elements as well as resource limitations. Material and methods: CKD women who needed dialysis in pregnancy over the period 2002–2014 and had with complete demographic and outcome data were included in this retrospective study. Clinical background, renal function during pregnancy, dialysis schedule, and clinical outcomes were reviewed. Results: Forty pregnancies in women with CKD who needed dialysis in pregnancy (39 singleton and one twin pregnancy) were studied: All patients were treated with hemodialysis. Thirty-nine patients had CKD stages 4 or 5 at referral; only one patient was of stage 3b. Dialysis was considered as indicated in the presence of fluid overload, unresponsive hypertension in the setting of advanced CKD, or when blood urea nitrogen values were increased to around 50 mg/dL. However, the initiation of dialysis was often delayed by days or weeks. The main reason for delaying the initiation of dialysis was patient (and family) refusal to start treatment. All patients were treated with thrice weekly dialysis, in 3–5 h sessions, with a target urea of <100 mg/dL. The number of hours on dialysis did not impact pregnancy outcomes. Ten pregnancies ended in miscarriages (8 spontaneous), 29 in pre-term delivery, and 1 in term delivery. Fifteen women were diagnosed with preeclampsia, one with eclampsia, and one with HELLP (hemolysis, elevated liver enzymes, low platelets,) syndrome. Twenty-four of the neonates survived (77.4% of live births); six singletons and one twin died as a consequence of prematurity. Two neonates displayed malformations: cleft palate with ear anomalies and duodenal atresia. Conclusions: CKD requiring hemodialysis in pregnancy is associated with a high frequency of complications; in the setting of delayed start and of thrice-weekly hemodialysis, dialysis schedules do not appear to influence outcomes. Full article
Open AccessArticle
Renal Consequences of Gestational Diabetes Mellitus in Term Neonates: A Multidisciplinary Approach to the DOHaD Perspective in the Prevention and Early Recognition of Neonates of GDM Mothers at Risk of Hypertension and Chronic Renal Diseases in Later Life
J. Clin. Med. 2019, 8(4), 429; https://doi.org/10.3390/jcm8040429
Received: 5 February 2019 / Revised: 14 March 2019 / Accepted: 25 March 2019 / Published: 28 March 2019
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Abstract
Fetal exposure to gestational diabetes mellitus (GDM) seems to stimulate a negative impact on the kidneys. Renal volumes and urinary biomarkers of renal function and tubular impairment and injury were evaluated in 30–40-day old newborns of GDM mothers (n = 139) who [...] Read more.
Fetal exposure to gestational diabetes mellitus (GDM) seems to stimulate a negative impact on the kidneys. Renal volumes and urinary biomarkers of renal function and tubular impairment and injury were evaluated in 30–40-day old newborns of GDM mothers (n = 139) who needed insulin therapy during pregnancy. We found that neonates of mothers who maintained strict control over normoglycemia (n = 65) during pregnancy and fulfilled the other criteria of the GDM management program showed no differences compared to control (n = 55). Conversely, those (n = 74), whose mothers did not maintain glycemic control and were not compliant to the management program, exhibited significantly lower levels of renal volumes and higher activity of N-acetyl-β-d-glucosaminidase and cathepsin B. Differences due to maternal pre-gestational and gestational body mass index (BMI) as well as to maternal weight gain were demonstrated. Our findings indicate that a multidisciplinary approach, which involves an appropriate management of GDM, prevents the negative effects of GDM on the kidneys at 30–40 days of postnatal age, indicating the fundamental role of glycemic control, as well as of an adequate range of maternal weight gain. Total renal volume, cortical volume, and urinary activity of N-acetyl-β-d-glucosaminidase and cathepsin B may be suggested as indicators for the early recognition of GDM neonates at long-term risk of hypertension and kidney disease. Full article
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Open AccessArticle
Confidence in Women’s Health: A Cross Border Survey of Adult Nephrologists
J. Clin. Med. 2019, 8(2), 176; https://doi.org/10.3390/jcm8020176
Received: 9 January 2019 / Revised: 26 January 2019 / Accepted: 30 January 2019 / Published: 3 February 2019
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Abstract
A range of women’s health issues are intimately related to chronic kidney disease, yet nephrologists’ confidence in counseling or managing these issues has not been evaluated. The women’s health working group of Cure Glomerulonephropathy (CureGN), an international prospective cohort study of glomerular disease, [...] Read more.
A range of women’s health issues are intimately related to chronic kidney disease, yet nephrologists’ confidence in counseling or managing these issues has not been evaluated. The women’s health working group of Cure Glomerulonephropathy (CureGN), an international prospective cohort study of glomerular disease, sought to assess adult nephrologists’ training in, exposure to, and confidence in managing women’s health. A 25-item electronic questionnaire was disseminated in the United States (US) and Canada via CureGN and Canadian Society of Nephrology email networks and the American Society of Nephrology Kidney News. Response frequencies were summarized using descriptive statistics. Responses were compared across provider age, gender, country of practice, and years in practice using Pearson’s chi-squared test or Fisher’s exact test. Among 154 respondents, 53% were women, 58% practiced in the US, 77% practiced in an academic setting, and the median age was 41–45 years. Over 65% of respondents lacked confidence in women’s health issues, including menstrual disorders, preconception counseling, pregnancy management, and menopause. Most provided contraception or preconception counseling to less than one woman per month, on average. Only 12% had access to interdisciplinary pregnancy clinics. Finally, 89% felt that interdisciplinary guidelines and/or continuing education seminars would improve knowledge. Participants lacked confidence in both counseling and managing women’s health. Innovative approaches are warranted to improve the care of women with kidney disease and might include the expansion of interdisciplinary clinics, the development of case-based teaching materials, and interdisciplinary treatment guidelines focused on this patient group. Full article
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Review

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Open AccessReview
The Extended Use of Eculizumab in Pregnancy and Complement Activation–Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys—The Future Is Now?
J. Clin. Med. 2019, 8(3), 407; https://doi.org/10.3390/jcm8030407
Received: 16 February 2019 / Revised: 14 March 2019 / Accepted: 19 March 2019 / Published: 24 March 2019
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Abstract
Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence [...] Read more.
Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence of complement activation affecting both maternal and fetal kidneys during pregnancy and causing long-term adverse outcomes. Several novel drugs have been recently developed for blocking the complement cascade, including purified plasma proteins, new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Eculizumab, the humanized monoclonal IgG2/4-antibody targeting C5 was approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of two rare diseases: PNH in 2007 and aHUS in 2011. There is an increasing number of publications of successful use of eculizumab for off-label indications, e.g., in pregnant women with antiphospholipid syndrome, sickle-cell anemia, and HELLP syndrome. These severe diseases are associated with both high maternal and fetal morbidity and mortality rate and substantial prematurity. Eculizumab has considerably improved overall outcome of patients with PNH and aHUS, enabling safe pregnancy for many women. Prolongation of pregnancy and the use of eculizumab, even for only a few weeks, may protect not only maternal renal function, but also alleviate acute and long-term renal consequences of prematurity in offspring. Full article
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Open AccessReview
Maternal Venous Hemodynamic Dysfunction in Proteinuric Gestational Hypertension: Evidence and Implications
J. Clin. Med. 2019, 8(3), 335; https://doi.org/10.3390/jcm8030335
Received: 1 February 2019 / Revised: 26 February 2019 / Accepted: 5 March 2019 / Published: 11 March 2019
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Abstract
This review summarizes current knowledge from experimental and clinical studies on renal function and venous hemodynamics in normal pregnancy, in gestational hypertension (GH) and in two types of preeclampsia: placental or early-onset preeclampsia (EPE) and maternal or late-onset (LPE) preeclampsia, presenting at <34 [...] Read more.
This review summarizes current knowledge from experimental and clinical studies on renal function and venous hemodynamics in normal pregnancy, in gestational hypertension (GH) and in two types of preeclampsia: placental or early-onset preeclampsia (EPE) and maternal or late-onset (LPE) preeclampsia, presenting at <34 weeks and ≥34 weeks respectively. In addition, data from maternal venous Doppler studies are summarized, showing evidence for (1) the maternal circulation functioning closer to the upper limits of capacitance than in non-pregnant conditions, with intrinsic risks for volume overload, (2) abnormal venous Doppler measurements obtainable in preeclampsia, more pronounced in EPE than LPE, however not observed in GH, and (3) abnormal venous hemodynamic function installing gradually from first to third trimester within unique pathways of general circulatory deterioration in GH, EPE and LPE. These associations have important clinical implications in terms of screening, diagnosis, prevention and management of gestational hypertensive diseases. They invite for further hypothesis-driven research on the role of retrograde venous congestion in the etiology of preeclampsia-related organ dysfunctions and their absence in GH, and also challenge the generally accepted view of abnormal placentation as the primary cause of preeclampsia. The striking similarity between abnormal maternal venous Doppler flow patterns and those observed at the ductus venosus and other abdominal veins of the intra-uterine growth restricted fetus, also invites to explore the role of venous congestion in the intra-uterine programming of some adult diseases. Full article
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Open AccessReview
Fetal Toxicity of Immunosuppressive Drugs in Pregnancy
J. Clin. Med. 2018, 7(12), 552; https://doi.org/10.3390/jcm7120552
Received: 30 October 2018 / Revised: 5 December 2018 / Accepted: 11 December 2018 / Published: 15 December 2018
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Abstract
Women affected by autoimmune diseases, organ transplantation, or neoplasia need to continue immunosuppressive treatment during pregnancy. In this setting, not only a careful planning of pregnancy, but also the choice of drugs is critical to preventing maternal complications and minimizing the fetal risks. [...] Read more.
Women affected by autoimmune diseases, organ transplantation, or neoplasia need to continue immunosuppressive treatment during pregnancy. In this setting, not only a careful planning of pregnancy, but also the choice of drugs is critical to preventing maternal complications and minimizing the fetal risks. Some immunosuppressive drugs are teratogenic and should be replaced even before the pregnancy, while other drugs need to be managed with caution to prevent fetal risks, including miscarriage, intrauterine growth restriction, prematurity, and low birth weight. In particular, the increasing use of biologic agents raises the question of their compatibility with reproduction. In this review we present data on the indication and safety in pregnancy of the most frequently used immunosuppressive drugs. Full article
Open AccessReview
Pregnancy in Chronic Kidney Disease: Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Different CKD Stages and Phases
J. Clin. Med. 2018, 7(11), 415; https://doi.org/10.3390/jcm7110415
Received: 7 October 2018 / Revised: 28 October 2018 / Accepted: 31 October 2018 / Published: 5 November 2018
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Abstract
Pregnancy is possible in all phases of chronic kidney disease (CKD), but its management may be difficult and the outcomes are not the same as in the overall population. The prevalence of CKD in pregnancy is estimated at about 3%, as high as [...] Read more.
Pregnancy is possible in all phases of chronic kidney disease (CKD), but its management may be difficult and the outcomes are not the same as in the overall population. The prevalence of CKD in pregnancy is estimated at about 3%, as high as that of pre-eclampsia (PE), a better-acknowledged risk for adverse pregnancy outcomes. When CKD is known, pregnancy should be considered as high risk and followed accordingly; furthermore, since CKD is often asymptomatic, pregnant women should be screened for the presence of CKD, allowing better management of pregnancy, and timely treatment after pregnancy. The differential diagnosis between CKD and PE is sometimes difficult, but making it may be important for pregnancy management. Pregnancy is possible, even if at high risk for complications, including preterm delivery and intrauterine growth restriction, superimposed PE, and pregnancy-induced hypertension. Results in all phases are strictly dependent upon the socio-sanitary system and the availability of renal and obstetric care and, especially for preterm children, of intensive care units. Women on dialysis should be aware of the possibility of conceiving and having a successful pregnancy, and intensive dialysis (up to daily, long-hours dialysis) is the clinical choice allowing the best results. Such a choice may, however, need adaptation where access to dialysis is limited or distances are prohibitive. After kidney transplantation, pregnancies should be followed up with great attention, to minimize the risks for mother, child, and for the graft. A research agenda supporting international comparisons is highly needed to ameliorate or provide knowledge on specific kidney diseases and to develop context-adapted treatment strategies to improve pregnancy outcomes in CKD women. Full article
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Open AccessReview
Acute Kidney Injury in Pregnancy: The Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Prevention and Care of Pregnancy-Related AKI, in the Year Dedicated to Women and Kidney Diseases
J. Clin. Med. 2018, 7(10), 318; https://doi.org/10.3390/jcm7100318
Received: 17 August 2018 / Revised: 18 September 2018 / Accepted: 19 September 2018 / Published: 1 October 2018
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Abstract
Pregnancy-related acute kidney injury (pAKI), preeclampsia (PE), and the hypertensive disorders of pregnancy are closely related conditions, which are, in turn, frequently linked to pre-existing and often non-diagnosed chronic kidney disease (CKD). The current literature and research mainly underline the effects of pregnancy [...] Read more.
Pregnancy-related acute kidney injury (pAKI), preeclampsia (PE), and the hypertensive disorders of pregnancy are closely related conditions, which are, in turn, frequently linked to pre-existing and often non-diagnosed chronic kidney disease (CKD). The current literature and research mainly underline the effects of pregnancy complications on the offspring; this review strongly emphasizes the maternal health as well. These conditions not only negatively affect pregnancy outcomes, but have a relevant effect on the future health of affected mothers and their children. Therefore, dedicated diagnostic and follow-up programs are needed, for optimizing materno-foetal health and reducing the impact of pregnancy-related problems in the mothers and in the new generations. This narrative review, performed on the occasion of the 2018 World Kidney Day dedicated to women’s health, focuses on three aspects of the problem. Firstly, the risk of AKI in the hypertensive disorders of pregnancy (the risk is the highest in developing countries; however PE is the main cause of pregnancy related AKI worldwide). Secondly, the effect of AKI and the hypertensive disorders of pregnancy on the development of CKD in the mother and offspring: long-term risks are increased; the entity and the trajectories are still unknown. Thirdly, the role of CKD in the pathogenesis of AKI and the hypertensive disorders of pregnancy: CKD is a major risk factor and the most important element in the differential diagnosis; pregnancy is a precious occasion for early diagnosis of CKD. Higher awareness on the importance of AKI in pregnancy is needed to improve short and long term outcomes in mothers and children. Full article
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Open AccessReview
A Systematic Review on Materno-Foetal Outcomes in Pregnant Women with IgA Nephropathy: A Case of “Late-Maternal” Preeclampsia?
J. Clin. Med. 2018, 7(8), 212; https://doi.org/10.3390/jcm7080212
Received: 1 July 2018 / Revised: 9 August 2018 / Accepted: 10 August 2018 / Published: 11 August 2018
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Abstract
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 [...] Read more.
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. Full article
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Other

Open AccessCase Report
Mitochondrial Disease (MELAS Syndrome) Discovered at the Start of Pregnancy in a Patient with Advanced CKD: A Clinical and Ethical Challenge
J. Clin. Med. 2019, 8(3), 303; https://doi.org/10.3390/jcm8030303
Received: 29 January 2019 / Revised: 23 February 2019 / Accepted: 25 February 2019 / Published: 4 March 2019
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Abstract
Pregnancy is a challenge in the life of a woman with chronic kidney disease (CKD), but also represents an occasion for physicians to make or reconsider diagnosis of kidney disease. Counselling is particularly challenging in cases in which a genetic disease with a [...] Read more.
Pregnancy is a challenge in the life of a woman with chronic kidney disease (CKD), but also represents an occasion for physicians to make or reconsider diagnosis of kidney disease. Counselling is particularly challenging in cases in which a genetic disease with a heterogeneous and unpredictable phenotype is discovered in pregnancy. The case reported regards a young woman with Stage-4 CKD, in which “Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes” (MELAS syndrome), was diagnosed during an unplanned pregnancy. A 31-year-old Caucasian woman, being followed for Stage-4 CKD, sought her nephrologist’s advice at the start of an unplanned pregnancy. Her most recent data included serum creatinine 2–2.2 mg/dL, Blood urea nitrogen (BUN) 50 mg/dL, creatinine clearance 20–25 mL/min, proteinuria at about 2 g/day, and mild hypertension which was well controlled by angiotensin-converting enzyme inhibitors (ACEi); her body mass index (BMI) was 21 kg/m2 (height 152 cm, weight 47.5 kg). Her medical history was characterized by non-insulin-dependent diabetes mellitus (at the age of 25), Hashimoto’s thyroiditis, and focal segmental glomerulosclerosis. The patient’s mother was diabetic and had mild CKD. Mild hearing impairment and cardiac hypertrophy were also detected, thus leading to suspect a mitochondrial disease (i.e., MELAS syndrome), subsequently confirmed by genetic analysis. The presence of advanced CKD, hypertension, and proteinuria is associated with a high, but difficult to quantify, risk of preterm delivery and progression of kidney damage in the mother; MELAS syndrome is per se associated with an increased risk of preeclampsia. Preterm delivery, associated with neurological impairment and low nephron number can worsen the prognosis of MELAS in an unpredictable way. This case underlines the importance of pregnancy as an occasion to detect CKD and reconsider diagnosis. It also suggests that mitochondrial disorders should be considered in the differential diagnosis of kidney impairment in patients who display an array of other signs and symptoms, mainly type-2 diabetes, kidney disease, and vascular problems, and highlights the difficulties encountered in counselling and the need for further studies on CKD in pregnancy. Full article
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Open AccessCase Report
Dialysis or a Plant-Based Diet in Advanced CKD in Pregnancy? A Case Report and Critical Appraisal of the Literature
J. Clin. Med. 2019, 8(1), 123; https://doi.org/10.3390/jcm8010123
Received: 8 December 2018 / Revised: 7 January 2019 / Accepted: 8 January 2019 / Published: 20 January 2019
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Abstract
Pregnancy is increasingly reported in chronic kidney disease (CKD), reflecting higher awareness, improvements in materno-foetal care, and a more flexible attitude towards “allowing” pregnancy in the advanced stages of CKD. Success is not devoid of problems and an important grey area regards the [...] Read more.
Pregnancy is increasingly reported in chronic kidney disease (CKD), reflecting higher awareness, improvements in materno-foetal care, and a more flexible attitude towards “allowing” pregnancy in the advanced stages of CKD. Success is not devoid of problems and an important grey area regards the indications for starting dialysis (by urea level, clinical picture, and residual glomerular filtration rate) and for dietary management. The present case may highlight the role of plant-based diets in dietary management in pregnant CKD women, aimed at retarding dialysis needs. The case. A 28-year-old woman, affected by glomerulocystic disease and unilateral renal agenesis, in stage-4 CKD, was referred at the 6th week of amenorrhea: she weighed 40 kg (BMI 16.3), was normotensive, had no sign of oedema, her serum creatinine was 2.73 mg/dL, blood urea nitrogen (BUN) 35 mg/dL, and proteinuria 200 mg/24 h. She had been on a moderately protein-restricted diet (about 0.8 g/kg/real body weight, 0.6 per ideal body weight) since childhood. Low-dose acetylsalicylate was added, and a first attempt to switch to a protein-restricted supplemented plant-based diet was made and soon stopped, as she did not tolerate ketoacid and aminoacid supplementation. At 22 weeks of pregnancy, creatinine was increased (3.17 mg/dL, BUN 42 mg/dL), dietary management was re-discussed and a plant-based non-supplemented diet was started. The diet was associated with a rapid decrease in serum urea and creatinine; this favourable effect was maintained up to the 33rd gestational week when a new rise in urea and creatinine was observed, together with signs of cholestasis. After induction, at 33 weeks + 6 days, she delivered a healthy female baby, adequate for gestational age (39th centile). Urea levels decreased after delivery, but increased again when the mother resumed her usual mixed-protein diet. At the child’s most recent follow-up visit (age 4 months), development was normal, with normal weight and height (50th–75th centile). In summary, the present case confirms that a moderate protein-restricted diet can be prescribed in pregnancies in advanced CKD without negatively influencing foetal growth, supporting the importance of choosing a plant-based protein source, and suggests focusing on the diet’s effects on microcirculation to explain these favourable results. Full article
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Open AccessCase Report
Acute IgA-Dominant Glomerulonephritis Associated with Syphilis Infection in a Pregnant Teenager: A New Disease Association
J. Clin. Med. 2019, 8(1), 114; https://doi.org/10.3390/jcm8010114
Received: 22 December 2018 / Revised: 8 January 2019 / Accepted: 14 January 2019 / Published: 18 January 2019
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Abstract
Chronic kidney disease (CKD) is increasingly recognized as a risk factor in pregnancy; the differential diagnosis between CKD and preeclampsia (PE) may be of pivotal importance for pregnancy management and for early treatment of CKD. Acknowledging this connection may be useful also in [...] Read more.
Chronic kidney disease (CKD) is increasingly recognized as a risk factor in pregnancy; the differential diagnosis between CKD and preeclampsia (PE) may be of pivotal importance for pregnancy management and for early treatment of CKD. Acknowledging this connection may be useful also in a wider context, such as in the case reported in this paper, which for the first time describes an association between syphilis infection and IgA-dominant glomerulonephritis. A 16-year-old woman, referred to a general hospital due to a seizure, was found to be unknowingly pregnant. Based on hypertension and nephrotic proteinuria, she was initially diagnosed with PE. Immunological tests, as well as hepatitis and HIV tests showed negative results. However, secondary syphilis was diagnosed. In discordance with the PE diagnosis, urinalysis showed glomerular microhematuria with cellular casts. Proteinuria and hypertension did not remit after delivery, which was made via caesarean section, due to uncontrolled hypertension, at an estimated gestational age of 29 weeks. A male baby, weighing 1.1 kg (6.5 centile) was born. The baby was hospitalized in the neonatal intensive care unit, where he developed subependymal hemorrhage and thrombocytopenia, and neonatal syphilis was diagnosed. The mother underwent a kidney biopsy one week after delivery, leading to the diagnosis of IgA-dominant postinfectious glomerulonephritis. Mother and child were treated with support and antibiotic therapy, and were discharged in good clinical conditions four weeks later. Four months after delivery, the mother was normotensive without therapy, with normal kidney function and without hematuria or proteinuria. In conclusion, this case suggests that IgA-dominant postinfectious glomerulonephritis should be added to the spectrum of syphilis-associated glomerulonephritides, and underlines the need for a careful differential diagnosis with CKD in all cases of presumed PE. While diagnosis relies on kidney biopsy, urinary sediment, a simple and inexpensive test, can be the first step in distinguishing PE from other nephropathies. Full article
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Open AccessCase Report
Fetal Renal Echogenicity Associated with Maternal Focal Segmental Glomerulosclerosis: The Effect of Transplacental Transmission of Permeability Factor suPAR
J. Clin. Med. 2018, 7(10), 324; https://doi.org/10.3390/jcm7100324
Received: 1 August 2018 / Revised: 22 September 2018 / Accepted: 1 October 2018 / Published: 4 October 2018
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Abstract
We report a case of a pregnant woman with nephrotic syndrome due to biopsy-proven focal segmental glomerulosclerosis (FSGS) whose fetus developed echogenic kidneys and severe oligohydramnios by 27 weeks of gestation. Maternal treatment with prednisone resulted in normalization of the amniotic fluid indices [...] Read more.
We report a case of a pregnant woman with nephrotic syndrome due to biopsy-proven focal segmental glomerulosclerosis (FSGS) whose fetus developed echogenic kidneys and severe oligohydramnios by 27 weeks of gestation. Maternal treatment with prednisone resulted in normalization of the amniotic fluid indices and resolution of fetal renal echogenicity. The newborn was noted to have transient renal dysfunction and proteinuria, resolving by 6 weeks postpartum. The transplacental passage of permeability factors is postulated to have caused both the fetal and newborn renal presentation, with significantly elevated levels of soluble urokinase-type plasminogen activator receptor (suPAR) noted in the cord blood. This case documents the transplacental maternal-fetal transmission of suPAR, demonstrating the potential for maternal-fetal transmission of deleterious, disease-causing entities, and adds to the differential diagnosis of fetal echogenic kidneys. Further, this is the first documentation of a fetal response to maternal systemic therapy. Full article
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