Adherence to the Mediterranean Diet Improves Fatty Acids Profile in Pediatric Patients with Idiopathic Nephrotic Syndrome.

The fatty acid profiles of patients with idiopathic nephrotic syndrome (INS) are different from that of healthy controls, even during remission, revealing an increase of the pro-inflammatory omega 6 series. It is still unknown whether the concomitance of nephrotic syndrome affects the potential positive effects of the Mediterranean diet on the levels of omega 3 and 6 fatty acids. We performed a cross-sectional study to evaluate the association between the adherence to the Mediterranean diet and fatty acid profile in 54 children with INS. The dietary habits were assessed through the validated Kidmed questionnaire. Patients with higher adherence had lower levels of linoleic acid and total omega-6. Moreover, a negative correlation between proteinuria and the anti-inflammatory omega-3 series was found. In conclusion, patients with INS with proteinuria and low adherence to the Mediterranean diet have an imbalance in the omega-6/omega-3 ratio that may benefit from following the Mediterranean diet.

Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study.

Kidney disease affects 10% of the world population and is associated with increased mortality. Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children, often failing standard immunosuppression. Here, we report the results of a prospective study to investigate the immunological impact and safety of a gluten-free and dairy-free (GF/DF) diet in children with SRNS. The study was organized as a four-week summer camp implementing a strict GF/DF diet with prospective collection of blood, urine and stool in addition to whole exome sequencing WES of DNA of participants. Using flow cytometry, proteomic assays and microbiome metagenomics, we show that GF/DF diet had a major anti-inflammatory effect in all participants both at the protein and cellular level with 4-fold increase in T regulatory/T helper 17 cells ratio and the promotion of a favorable regulatory gut microbiota. Overall, GF/DF can have a significant anti-inflammatory effect in children with SRNS and further trials are warranted to investigate this potential dietary intervention in children with SRNS.

Evaluation of Concentration Errors and Inappropriate Dose Tailoring of Tacrolimus Caused by Sampling-Time Deviations in Pediatric Patients With Primary Nephrotic Syndrome.

BACKGROUND: Tacrolimus dosing is routinely tailored based on its trough level (C0) drawn by therapeutic drug monitoring in pediatric patients with primary nephrotic syndrome. However, this concentration is often inaccurate owing to inappropriate practice, such as deviation of sampling time (DST). The quantitative relationship between DST and C0 remains unclear. METHODS: Tacrolimus concentration at nominal sampling times (12 hours after last dose) and 32 deviation scenarios (12 ± 4 hours every 15 minutes) was predicted using a previously validated population pharmacokinetic model based on 162 scenarios of 100 primary nephrotic syndrome patients involved in the population pharmacokinetic model and derived virtual patients. Concentration error (CE) and relative CE (RCE) were evaluated, and the correlation between DST and RCE was evaluated by subgroup analysis using linear regression. Ultimately, the inappropriate dosing possibly misled by incorrect C0 was simulated in a real-patient cohort according to the target range (5-10 ng/mL). RESULTS: Approximately 7% of RCE was caused at every 1-hour of DST. DST was the most major contributor of RCE (r = 0.773-0.804). Patients with early sampling, older age, high body weight, high dose, low aspartate transaminase level, high corticosteroid dose, and without combination of azole antifungal agents were revealed to have high RCE. Approximately 7%-36% and 9%-25% of inappropriate dose tailoring may be caused by early and delayed sampling, respectively. In addition, patients with early sampling or high-dose tacrolimus had a higher risk of inappropriate dosing than patients with delayed sampling [hazard ratio = 1.53, 95% confidence interval (CI): 1.03-2.27, P = 0.048], and low-dose tacrolimus (P < 0.0001). CONCLUSIONS: A moderate bias of concentration and dose tailoring was revealed within 4 hours of DST. In addition, a high risk of bias was found in patients with early sampling and high-dose tacrolimus.

Round Table Discussion.

The 1st International Carnitine Working Group concluded with a round table discussion addressing several areas of relevance. These included the design of future studies that could increase the amount of evidence-based data about the role of carnitine in the treatment of fatty acid oxidation defects, for which substantial controversy still exists. There was general consensus that future trials on the effect of carnitine in disorders of fatty acid oxidation should be randomized, double-blinded, multicentered and minimally include the following diagnoses: medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency. Another area that generated interest was trials of carnitine in cardiomyopathy and, especially, the use of biomarkers to identify patients at greater risk of cardiotoxicity following treatment with anthracyclines. The possibility that carnitine treatment may lead to improvements in autistic behaviors was also discussed, although the evidence is still not sufficient to make any firm conclusions in this regard. Preliminary data on carnitine levels in children and adolescents with primary hypertension, low birth weight and nephrotic syndrome was also presented. Lastly, the panelists stressed that there remains an objective need to harmonize the terminology used to describe carnitine deficiencies (e.g., primary, secondary and systemic deficiency).

[Nutritional management of kidney diseases in children].

The prevalence of various kidney diseases in children remains high in recent decades. Adequate nutrition management can enhance the effectiveness of drug treatment, slow the frequency of relapses andprevent the progression of the disease. The article is devoted to modern approaches to diet therapy in various kidney diseases in children with the defeat of tubular and glomerular appa ratus. For the first time the therapeutic diets for children with various kidney diseases are presented. Particular attention is paid to diet therapy in nephrotic syndrome (steroid-responsive and steroid-refractory). Dietary approaches with modern formulas for enteral nutrition in cases of steroid therapy complications in children with renal insufficiency (in predialysis stage and on dialysis) are described. Differentiated nutritional approaches for patients with different types of crystalluria are separately presented.

The Effect of a Gluten-Free Diet in Children With Difficult-to-Manage Nephrotic Syndrome.

Case reports have linked childhood nephrotic syndrome to food sensitivity, including gluten. We report our experience with 8 children (6 boys, 2 girls; age at implementation of special diet 2-14 years) with difficult-to-manage nephrotic syndrome who were placed on a gluten-free diet for 3.4 ± 4.3 years (range, 0.6-14 years) and who had clinical improvement enabling reduction or discontinuation in steroid dosage.

Effects of gluten-free, dairy-free diet on childhood nephrotic syndrome and gut microbiota.

Emerging evidence suggests an association between food sensitivity and gut microbiota in children with nephrotic syndrome. Diminished proteinuria resulted from eliminating cow's milk and the use of an oligoantigenic diet which excluded gluten, especially in patients with immune-related conditions, i.e., celiac disease and nephrotic syndrome. The mechanisms underlying the association of diet, gut microbiota, and dysregulation of the immune system are unknown. Gut microbiota is influenced by a number of factors including diet composition and other environmental epigenetic exposures. The imbalance in gut microbiota may be ameliorated by gluten-free and dairy-free diets. Gluten-free diet increased the number of unhealthy bacteria while reducing bacterial-induced cytokine production of IL-10. Thus, gluten-free diet may influence the composition and immune function of gut microbiota and should be considered a possible environmental factor associated with immune-related disease, including nephrotic syndrome. Furthermore, the imbalance of gut microbiota may be related to the development of cow's milk protein allergy. Investigations are needed to fill the gaps in our knowledge concerning the associations between the gut microbiome, environmental exposures, epigenetics, racial influences, and the propensity for immune dysregulation with its inherent risk to the developing individual.

[Nutrition of patients with stomach acid-dependent pathology and inflammatory diseases of the urogenital system].

In work some, often meeting nosological forms urogenithal surgical diseases which last years frequently proceed against gastritises, stomach ulcer of a stomach and 12-perstnoj guts owing to increase of occurrence of the last are presented. For treatment various medicamentous schemes, which do-polnjajutsja rational diet-correction for the purpose of increase efficaci and qualities of treatment are used. The work purpose--to present features ratsional pathogenetic correctic a food at persons from an aggravation acid-deprndent to a pathology against constant reception prepara apropos urogenithal diseases.

Unusual presentation of celiac disease presenting with renal complications.

Celiac disease is a chronic inflammatory condition of small intestine resulting due to sensitivity to wheat protein gluten. Most patients in the childhood present with primary gastrointestinal complaints. The authors present here two young girls with renal complaints later diagnosed to have celiac disease.

Relapse or worsening of nephrotic syndrome in idiopathic membranous nephropathy can occur even though the glomerular immune deposits have been eradicated.

BACKGROUND: Relapse or worsening of nephrotic syndrome (NS) in idiopathic membranous nephropathy (IMN) is generally assumed to be due to recurrent disease. Here we document that often that may not be the case. SUBJECTS AND METHODS: This is a prospective study of 7 consecutive IMN patients whose renal status improved, then worsened after completing a course of immunosuppressive therapy. Each underwent detailed testing and repeat kidney biopsy. RESULTS: In 4 patients (group A), the biopsy showed recurrent IMN (fresh subepithelial deposits). Immunosuppressive therapy was begun. In the other 3 patients (group B), the biopsy showed that the deposits had been eradicated. However, the glomerular basement membrane (GBM) was thickened and vacuolated. Immunosuppressive therapy was withheld. Groups A and B were comparable except that group B had very high intakes of salt and protein, based on 24-hour urine testing. Reducing their high salt intake sharply lowered proteinuria to the subnephrotic range and serum creatinine stabilized. CONCLUSION: This work is the first to demonstrate that relapse/worsening of NS can occur in IMN even though the GBM deposits have been eradicated. High salt and protein intake in combination with thickened and vacuolated GBM appears to be the mechanism.

Looking at appearance of urine before performing a renal biopsy in nephrotic syndrome.

Chyluria results from an abnormal connection between lymphatic bed and urinary tract, causing lymph leakage into the urine. The clinical picture often begins with the appearance of cloudy, milky urines accompanied by monolateral flank pain, malnutrition, weight loss and weakness. We report a case of chyluria that occurred in a young woman who was referred to our unit for nephrotic-range proteinuria. Before performing a renal biopsy, we found that urine analysis demonstrated a massive lipiduria. Therefore, we collected urine samples from each kidney with a selective ureteral catheterization, demonstrating a monolateral source of lipids and proteins. We suspended the renal biopsy and performed a lymphography that showed an inherited lymphangioma on the left lumbar lymphatic bed. Sclerosing solution instillation, renal pedicle lymphatic disconnection or laser therapy are invasive therapeutical options that may cause severe adverse effects. Instead of these procedures, a conservative therapy based on a low-fat diet supplemented with medium-chain triglycerides was chosen. This dietetic schedule was followed by complete resolution of proteinuria and lipiduria. The patient progressively gained body weight and improved quality of life. No relapses were observed after 3 years of follow-up. This case emphasizes the possible role of a noninvasive therapeutical option for patients with chyluria.

[Effectiveness of dietetic treatment in nephrotic syndrome]. / Eficacia del tratamiento dietético en el síndrome nefrótico.

We present the case of a male patient suffering from a primary amyloidosis and a nephrotic syndrome who came to dietotherapy clinic. In the first visit we made a nutritional record including an anthropometric evaluation, body composition, biochemistry, and food intake. The patient had an excess of body water, proteinuria, low plasma protein, albumin, prealbumin and HDL cholesterol levels, and high concentrations of total cholesterol, LDL and triglycerides. The consumption of protein and sodium was higher than the recommendation. An individualized diet was made. Six months later, his weight and the excess of body water decreased, but the fat free mass remained unchanged. The levels of albumin and prealbumin increased, the proteinuria decreased. Total cholesterol, LDL and triglycerides decreased until normal levels. Dietetary treatment in nephrotic syndrome is effective to decrease proteinuria, improve cholesterol and triglycerides levels, and to prevent malnutrition.

Improved outcomes in nephrotic syndrome.

Nephrotic syndrome can now be treated effectively in most cases. All patients should be treated with a low-salt diet, diuretics to reduce edema, and statins to normalize serum lipid concentrations. Patients with nephrotic syndrome are prone to deep vein thrombophlebitis, renal vein thrombosis, and pulmonary emboli. Depending on the condition, additional treatment may include corticosteroids, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), cyclosporine, cytotoxic agents, or mycophenolate.

[Treatment of nephrotic syndrome in the adult]. / A felnottkori nephrosis szindróma kezelése.

Approximately two-third of the cases of the adult nephrotic syndrome is caused by a primary glomerular disease, while the remaining one-third is caused by diabetes mellitus, autoimmune diseases, or amyloidosis. There are two different therapies to treat the syndrome: a general and a special treatment. The general treatment includes administering an appropriate diet (reduced intake of proteins and salt), use of diuretics and lipid-lowering drugs (primarily statins) and initiation of anticoagulant treatment, if required. It is generally necessary to administer angiotensin-convertase-enzyme inhibitors and angiotensin receptor blockers as well as initiate a symptomatic treatment to mitigate the loss of special binding-proteins. The special treatment involves the administration of immunosuppressive and cytostatic drugs. This therapy can be initiated only after the evaluation of renal histology and the overall risk status of the patient. Steroids are still the basic immunosuppressive drugs. Their use can be supplemented with other immunosuppressive or cytostatic treatment. In therapy resistant cases, however, new drugs like mycophenolate mofetil or rituximab can also be applied.

A soy protein diet alters hepatic lipid metabolism gene expression and reduces serum lipids and renal fibrogenic cytokines in rats with chronic nephrotic syndrome.

Nephrotic syndrome (NS) is characterized by the presence of proteinuria and hyperlipidemia. However, ingestion of soy protein has a hypolipidemic effect. The present study was designed to determine whether the ingestion of a 20% soy protein diet regulates the expression of hepatic sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), malic enzyme, beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase (r) and synthase (s), and LDL receptor (r), and to assess whether soy protein improves lipid and renal abnormalities in rats with chronic NS. Male Wistar rats were injected with vehicle or with puromycin aminonucleoside to induce NS and were fed either 20% casein or soy protein diets for 64 d. NS rats fed 20% soy protein had improved creatinine clearance and reduced proteinuria, hypercholesterolemia, hypertriglyceridemia, as well as VLDL-triglycerides and LDL cholesterol compared with NS rats fed the 20% casein diet. In addition, the soy protein diet decreased the incidence of glomerular sclerosis, and proinflammatory cytokines in kidney. Ingestion of the soy protein diet by control rats reduced the gene expression of SREBP-1, malic enzyme, FAS and increased HMG-CoAr, HMG-CoAs and LDLr. However, NS rats fed either casein or soy protein diets had low insulin concentrations with reductions in SREBP-1, FAS and malic enzyme expression compared with control rats fed the casein diet. NS rats fed the soy diet also had lower HMG-CoAr and LDLr mRNA levels than NS rats fed casein. In conclusion, the beneficial effects of soy protein on lipid metabolism are modulated in part by SREBP-1. However, in NS rats, the benefit may be through a direct effect of this protein on kidney rather than mediated by changes in expression of hepatic lipid metabolism genes.

CNP production in the kidney and effects of protein intake restriction in nephrotic syndrome.

C-type natriuretic peptide (CNP) possesses well-established cardiovascular properties. Although present in the mammalian kidney, CNP production in human kidney and its modulation in human renal disease remain less defined. We investigated the presence of CNP in normal human kidney and in patients with nephrotic syndrome (NS). We also addressed whether or not a low-protein diet (LPD) alters plasma CNP and urinary CNP excretion in NS. In situ hybridization studies demonstrated CNP mRNA expression in tubular cells and glomeruli of normal human kidneys. CNP immunoreactivity was positive in proximal, distal, and medullary collecting duct tubular cells in both controls and patients with NS. The ratios of plasma CNP and urinary CNP to creatinine were significantly higher in patients with NS compared with controls. Urinary CNP, but not plasma CNP, was significantly lowered in patients with NS after an LPD. Similarly, the ratios of urinary protein to creatinine and urinary albumin to creatinine, but not urinary guanosine 3',5'-cyclic monophosphate to creatinine, decreased significantly with an LPD. These data confirm and extend previous reports and demonstrate for the first time the presence of CNP in human kidney with NS. We also report increased plasma CNP concentration and urinary CNP excretion in NS patients and a significant reduction of CNP excretion with an LPD. Our findings demonstrate that CNP metabolism is altered in patients with NS and support the hypothesis that activation of renal CNP can be partially offset by an LPD. These results underscore that the beneficial effect of an LPD on protein excretion is paralleled by a substantial reduction in intrarenal CNP release.

Changes of protein kinetics in nephrotic patients.

Nephrotic patients show various abnormalities in protein kinetics. Plasma albumin levels and the total plasma albumin pool are reduced. The rate of hepatic absolute and fractional albumin synthesis are increased. Transferrin synthesis is also increased. Fibrinogen levels are elevated in nephrotic syndrome because of an increase in the hepatic synthesis. Regulation of albumin and fibrinogen synthesis seems to be coordinated. A low protein diet has been proposed as a therapeutic tool in nephrotic patients--clinical studies have shown that such a diet reduces proteinuria and increases renal survival. Nephrotic patients can adapt to moderate protein restriction with no sign of malnutrition and maintenance of a neutral nitrogen balance. Albumin and fibrinogen synthesis are ameliorated by dietary protein restriction and these changes are correlated with the beneficial effect of the diet on proteinuria.

[Dietary antioxidants and total antioxidant status in children with nephrotic syndrome]. / Spozycie substancji antyoksydacyjnych a calkowity potencjal antyoksydacyjny u dzieci chorych na zespól nerczycowy.

UNLABELLED: Several studies indicate the pathophysiological importance of reactive oxygen species in patients with nephrotic syndrome (NS). The present study was designed to determine the effect of dietary antioxidants on antioxidant enzymes (SOD, GPX, GR) activity and on total antioxidant status (TAS) in children with nephrotic syndrome. 36 children with NS (19 with first episode and 17 with relapse of NS) aged 4-16 were included into the study. Total antioxidant status was estimated using two-reagent Randox Total Antioxidant Status test in plasma. All patients had normal blood pressure, normal serum creatinine level and ingested a diet appropriate for age (with individual differences). Total antioxidant status was estimated using two-reagent Randox Total Antioxidant Status test in the plasma. Glutathione peroxidase (GPX), superperoxide dysmutase (SOD) and glutathione reductase (GR) activity was using antioxidant kits (Randox). A 3-day dietary intake record was obtained from each patient and then analyzed with computer program FOOD 2.0. Laboratory investigations were performed before steroid treatment. RESULTS: 1) in children with NS TAS was significantly reduced comparing to controls (0.84 +/- 0.14, 1.21 +/- 0.62 mmol/l, p = 0.002), 2) low manganese intake was found to have negative influence on TAS (TAS = 0.38 + 14.252*Mn, p > 0.001). 3) low intake of all components of antioxidant system was found: zinc (5.6 +/- 3.5 mg/kg b.w./24 h vs 8.6 +/- 4.0 mg/kg b.w./24 h), copper (0.021 +/- 0.013 mg/kg b.w./24 h vs 0.044 +/- 0.014 mg/kg b.w./24 h), manganese (0.029 +/- 0.0021 mg/kg b.w./24 h vs. 0.067 +/- 0.023 mg/kg b.w./24 h), vitamin E (0.15 +/- 0.04 mg/kg b.w./24 h vs 0.26 +/- 0.06 mg/kg b.w./24 h) and vitamin C (0.34 +/- 0.17 mg/kg b.w./24 h vs 0.87 +/- 0.19 mg/kg b.w./24 h). CONCLUSION: In children with NS reduced antioxidant protection maybe partly associated with low intake of some vital components of the antioxidant system.

Effects of dietary protein restriction on fibrinogen and albumin metabolism in nephrotic patients.

BACKGROUND: Nephrotic syndrome (NS) is characterized by profound changes in albumin and fibrinogen levels. Dietary protein restriction has been advocated in the treatment of patients with NS, but its effects on albumin and fibrinogen metabolism have not been fully elucidated. METHODS: We evaluated the effects of dietary protein restriction on endogenous leucine flux (ELF), fibrinogen and albumin metabolism in seven patients with NS who consumed either a normal protein diet (NPD; 1.20 +/- 0.06 g/kg/day), or a low protein diet (LPS; 0.66 +/- 0.04 g/kg/day) for four weeks. Seven normal subjects served as controls. The postabsorptive ELF value, fractional synthesis rate (FSR) and absolute synthesis rate (ASR) of both albumin and fibrinogen were evaluated during the last 120 minutes of a five-hour 5,5,5-D3-L-leucine infusion. RESULTS: During the NPD regimen. ELF was increased, serum albumin was reduced, plasma fibrinogen was increased, albumin FSR and ASR were both increased, fibrinogen FSR was normal, and fibrinogen ASR was greater in patients with NS compared to controls. In patients with NS the LPD regimen reduced proteinuria, ELF, albumin FSR and ASR, plasma fibrinogen levels, fibrinogen ASR, and increased serum ulbumin levels. Dietary-induced changes in albumin and fibrinogen synthesis were significantly correlated (r = 0.719, P < 0.05). CONCLUSIONS: Patients with NS treated with LPD show: (1) a reduction of proteinuria, albumin ASR and FSR, with an increase in serum albumin levels and its intravascular pool; (2) a decrease of fibrinogen ASR, with a reduction in both plasma fibrinogen levels and intravascular pool; and (3) a reduced rate of whole body proteolysis.