Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

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.

Nutrition care for chronic kidney disease during pregnancy: an updated review.

Cases of chronic kidney disease (CKD), including CKD in pregnant women, have increased globally in recent years. CKD during pregnancy is associated with a higher risk of adverse outcomes, including gestational hypertension, preeclampsia, intrauterine growth restriction, and preterm birth, among others. Nutrition plays a significant role in many metabolic and physiological changes during pregnancy. Women with CKD are at increased risk of nutrition deficiencies and metabolic issues than women without CKD. Currently, we lack evidence regarding metabolic and nutritional adaptations during pregnancy in women with CKD and how these adaptations relate to perinatal outcomes. In this review, dietary and supplementation recommendations for CKD in adults and pregnant women are summarized from current clinical guidelines. We present the main nutrition care practices that have been studied in CKD pregnancies. This review will be helpful to health professionals as a preliminary reference for nutrition assessment and therapy in pregnant women with CKD.

The microbiota composition of the offspring of patients with gestational diabetes mellitus (GDM).

The microbiota composition of the offspring of women with gestational diabetes mellitus (GDM), a common pregnancy complication, is still little known. We investigated whether the GDM offspring gut microbiota composition is associated with the maternal nutritional habits, metabolic variables or pregnancy outcomes. Furthermore, we compared the GDM offspring microbiota to the microbiota of normoglycemic-mother offspring. Fecal samples of 29 GDM infants were collected during the first week of life and assessed by 16S amplicon-based sequencing. The offspring's microbiota showed significantly lower α-diversity than the corresponding mothers. Earlier maternal nutritional habits were more strongly associated with the offspring microbiota (maternal oligosaccharide positively with infant Ruminococcus, maternal saturated fat intake inversely with infant Rikenellaceae and Ruminococcus) than last-trimester maternal habits. Principal coordinate analysis showed a separation of the infant microbiota according to the type of feeding (breastfeeding vs formula-feeding), displaying in breast-fed infants a higher abundance of Bifidobacterium. A few Bacteroides and Blautia oligotypes were shared by the GDM mothers and their offspring, suggesting a maternal microbial imprinting. Finally, GDM infants showed higher relative abundance of pro-inflammatory taxa than infants from healthy women. In conclusion, many maternal conditions impact on the microbiota composition of GDM offspring whose microbiota showed increased abundance of pro-inflammatory taxa.

Diet-Gut Microbiota Interactions and Gestational Diabetes Mellitus (GDM).

Medical nutritional therapy is the first-line approach in managing gestational diabetes mellitus (GDM). Diet is also a powerful modulator of the gut microbiota, whose impact on insulin resistance and the inflammatory response in the host are well known. Changes in the gut microbiota composition have been described in pregnancies either before the onset of GDM or after its diagnosis. The possible modulation of the gut microbiota by dietary interventions in pregnancy is a topic of emerging interest, in consideration of the potential effects on maternal and consequently neonatal health. To date, very few data from observational studies are available about the associations between diet and the gut microbiota in pregnancy complicated by GDM. In this review, we analyzed the available data and discussed the current knowledge about diet manipulation in order to shape the gut microbiota in pregnancy.

Dialysis or a Plant-Based Diet in Advanced CKD in Pregnancy? A Case Report and Critical Appraisal of the Literature.

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.

Changes in the gut microbiota composition during pregnancy in patients with gestational diabetes mellitus (GDM).

Gestational diabetes mellitus (GDM), a common pregnancy complication, is associated with an increased risk of maternal/perinatal outcomes. We performed a prospective observational explorative study in 41 GDM patients to evaluate their microbiota changes during pregnancy and the associations between the gut microbiota and variations in nutrient intakes, anthropometric and laboratory variables. GDM patients routinely received nutritional recommendations according to guidelines. The fecal microbiota (by 16S amplicon-based sequencing), was assessed at enrolment (24-28 weeks) and at 38 weeks of gestational age. At the study end, the microbiota α-diversity significantly increased (P < 0.001), with increase of Firmicutes and reduction of Bacteroidetes and Actinobacteria. Patients who were adherent to the dietary recommendations showed a better metabolic and inflammatory pattern at the study-end and a significant decrease in Bacteroides. In multiple regression models, Faecalibacterium was significantly associated with fasting glucose; Collinsella (directly) and Blautia (inversely) with insulin, and with Homeostasis-Model Assessment Insulin-Resistance, while Sutterella with C-reactive protein levels. Consistent with this latter association, the predicted metagenomes showed a correlation between those taxa and inferred KEGG genes associated with lipopolysaccharide biosynthesis. A higher bacterial richness and strong correlations between pro-inflammatory taxa and metabolic/inflammatory variables were detected in GDM patients across pregnancy. Collectively these findings suggest that the development of strategies to modulate the gut microbiota might be a potentially useful tool to impact on maternal metabolic health.

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.

Vegan-vegetarian low-protein supplemented diets in pregnant CKD patients: fifteen years of experience.

BACKGROUND: Pregnancy in women with advanced CKD becoming increasingly common. However, experience with low-protein diets in CKD patients in pregnancy is still limited. Aim of this study is to review the results obtained over the last 15 years with moderately restricted low-protein diets in pregnant CKD women (combining: CKD stages 3-5, proteinuria: nephrotic at any time, or > =1 g/24 at start or referral; nephrotic in previous pregnancy). CKD patients on unrestricted diets were employed for comparison. STUDY PERIOD: January, 2000 to September, 2015: 36 on-diet pregnancies (31 singleton deliveries, 3 twin deliveries, 1 pregnancy termination, 1 miscarriage); 47 controls (42 singleton deliveries, 5 miscarriages). The diet is basically vegan; since occasional milk and yoghurt are allowed, we defined it vegan-vegetarian; protein intake (0.6-0.8 g/Kg/day), keto-acid supplementation, protein-unrestricted meals (1-3/week) are prescribed according to CKD stage and nutritional status. Statistical analysis was performed as implemented on SPSS. RESULTS: Patients and controls were similar (p: ns) at baseline with regard to age (33 vs 33.5), referral week (7 vs 9), kidney function (CKD 3-5: 48.4 % vs 64.3 %); prevalence of hypertension (51.6 % vs 40.5 %) and proteinuria >3 g/24 h (16.1 % vs 12.2 %). There were more diabetic nephropathies in on-diet patients (on diet: 31.0 % vs controls 5.3 %; p 0.007 (Fisher)) while lupus nephropathies were non-significantly higher in controls (on diet: 10.3 % vs controls 23.7 %; p 0.28 (Fisher)). The incidence of preterm delivery was similar (<37 weeks: on-diet singletons 77.4 %; controls: 71.4 %). The incidence of other adverse pregnancy related outcomes was non-significantly lower in on-diet patients (early preterm delivery: on diet: 32.3 % vs controls 35.7 %; birth-weight = <1.500 g: on diet: 9.7 % vs controls 23.8 %). None of the singletons in the on-diet series died, while two perinatal deaths occurred among the controls (p = 0.505). The incidence of small for gestational age (SGA <10th centile) and/or extremely preterm babies (<28th week) was significantly lower in singletons from on-diet mothers than in controls (on diet: 12.9 % vs controls: 33.3 %; p: 0.04 (Fisher)). CONCLUSION: Moderate protein restriction in the context of a vegan-vegetarian supplemented diet is confirmed as a safe option in the management of pregnant CKD patients.

Low protein diets in patients with chronic kidney disease: a bridge between mainstream and complementary-alternative medicines?

Dietary therapy represents an important tool in the management of chronic kidney disease (CKD), mainly through a balanced reduction of protein intake aimed at giving the remnant nephrons in damaged kidneys a "functional rest". While dialysis, transplantation, and pharmacological therapies are usually seen as "high tech" medicine, non pharmacological interventions, including diets, are frequently considered lifestyle-complementary treatments. Diet is one of the oldest CKD treatments, and it is usually considered a part of "mainstream" management. In this narrative review we discuss how the lessons of complementary alternative medicines (CAMs) can be useful for the implementation and study of low-protein diets in CKD. While high tech medicine is mainly prescriptive, prescribing a "good" life-style change is usually not enough and comprehensive counselling is required; the empathic educational approach, on which CAMs are mainly, though not exclusively based, may support a successful personalized nutritional intervention.There is no gold-standard, low-protein diet for all CKD patients: from among a relatively vast choice, the best compliance is probably obtained by personalization. This approach interferes with the traditional RCT-based analyses which are grounded upon an assumption of equal preference of treatments (ideally blinded). Whole system approaches and narrative medicine, that are widely used in the study of CAMs, may offer ways to integrate EBM and personalised medicine in the search for innovative solutions respecting individualization, but gaining sound data, such as with partially-randomised patient preference trials.

Low-protein diets in CKD: how can we achieve them? A narrative, pragmatic review.

Low-protein diets (LPDs) have encountered various fortunes, and several questions remain open. No single study, including the famous Modification of Diet in Renal Disease, was conclusive and even if systematic reviews are in favour of protein restriction, at least in non-diabetic adults, implementation is lagging. LPDs are considered difficult, malnutrition is a threat and compliance is poor. LPDs have been reappraised in this era of reconsideration of dialysis indications and timing. The definition of a normal-adequate protein diet has shifted in the overall population from 1 to 1.2 to 0.8 g/kg/day. Vegan-vegetarian diets are increasingly widespread, thus setting the groundwork for easier integration of moderate protein restriction in Chronic Kidney Disease. There are four main moderately restricted LPDs (0.6 g/kg/day). Two of them require careful planning of quantity and quality of food: a 'traditional' one, with mixed proteins that works on the quantity and quality of food and a vegan one, which integrates grains and legumes. Two further options may be seen as a way to simplify LPDs while being on the safe side for malnutrition: adding supplements of essential amino and keto acids (various doses) allows an easier shift from omnivorous to vegan diets, while protein-free food intake allows for an increase in calories. Very-low-protein diets (vLPDs: 0.3 g/kg/day) combine both approaches and usually require higher doses of supplements. Moderately restricted LPDs may be adapted to virtually any cuisine and should be tailored to the patients' preferences, while vLPDs usually require trained, compliant patients; a broader offer of diet options may lead to more widespread use of LPDs, without competition among the various schemas.

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.

Severe diabetic nephropathy in type 1 diabetes and pregnancy--a case series.

BACKGROUND: Diabetes and nephropathy are important challenges during pregnancy, increasingly encountered because of the advances in maternal-fetal care. AIM: To evaluate the maternal and fetal outcomes recorded in "severe" diabetic nephropathy in type 1 diabetic patients referred to nephrological healtcare. METHODS: The study was performed in an outpatient unit dedicated to kidney diseases in pregnancy (with joint nephrological and obstetric follow-up and strict cooperation with the diabetes unit). 383 pregnancies were referred to the outpatient unit in 2000-2012, 14 of which were complicated by type 1 diabetes. The report includes 12 deliveries, including 2 pregnancies in 1 patient; one twin pregnancy; 2 spontaneous abortions were not included. All cases had long-standing type 1 diabetes (median of 21 (15-31) years), relatively high median age (35 (29-40) years) and end-organ damage (all patients presented laser-treated retinopathy and half of them clinical neuropathy). Median glomerular filtration rate (GFR) at referral was 67 ml/min (48-122.6), proteinuria was 1.6 g/day (0.1-6.3 g/day). RESULTS: Proteinuria steeply increased in 11/12 patients, reaching the nephrotic range in nine (6 above 5 g/day). One patient increased by 2 chronic kidney disease (CKD) stages. Support therapy included blood pressure and diabetes control, bed rest, and moderate protein restriction. All children were preterm (7 early preterm); early spontaneous labor occurred in 4/12 patients. All singletons were appropriate for gestational age and developed normally after birth. The male twin child died 6 days after birth (after surgery for great vessel transposition). CONCLUSIONS: Diabetic patients with severe diabetic nephropathy are still present a considerable challenge. Therefore, further investigations are required, particularly on proteinuria management and the occurrence of spontaneous labor.