The case for a ketogenic diet in the management of kidney disease.

Ketogenic diets have been widely used for weight loss and are increasingly used in the management of type 2 diabetes. Despite evidence that ketones have multiple positive effects on kidney function, common misconceptions about ketogenic diets, such as high protein content and acid load, have prevented their widespread use in individuals with impaired kidney function. Clinical trial evidence focusing on major adverse kidney events is sparse. The aim of this review is to explore the effects of a ketogenic diet, with an emphasis on the pleiotropic actions of ketones, on kidney health. Given the minimal concerns in relation to the potential renoprotective effects of a ketogenic diet, future studies should evaluate the safety and efficacy of ketogenic interventions in kidney disease.

Dietary Trichosporon mycotoxinivoron modulates ochratoxin-A induced altered performance, hepatic and renal antioxidant capacity and tissue injury in broiler chickens.

Ochratoxin A (OTA), an important fungal metabolite in foods and feeds has been shown to induce oxidative stress and cellular injuries to human and animal subjects. This study was designed to investigate the mode of action of a biological modifier Trichosporon mycotoxinivorans (TM), against OTA-mediated oxidative stress and tissue toxicity on broiler chickens. The birds were offered diets supplemented with OTA (0.15 and 0.3 mg/kg feed) and/or TM (0.5, 1.0 g/kg) for 42 days of age, and blood and tissue samples were collected to examine the oxidative stress, biochemical and histopathological parameters. Dietary OTA at all the tested levels induced the hepatic and renal tissue injury as indicated by significant decreased total antioxidant capacity in these organs along with significant decreased (p ≤ 0.05) serum concentrations of total proteins and albumin. The serum concentrations of alanine aminotransferase (ALT) and urea were significantly increased, and these observations were further supported by degenerative changes and increased relative weights of liver and kidneys. The dietary supplementation of TM at both tested levels relieved the detrimental impact of 0.15 and 0.3 mg OTA/kg on the studied parameters. The results of the study demonstrated that dietary TM significantly protects broiler chickens by reducing OTA-induced oxidative damage and tissue injury.

Deciphering nutritional interventions for podocyte structure and function.

Despite increasing awareness and therapeutic options chronic kidney disease (CKD) is still and important health problem and glomerular diseases constitute and important percentage of CKD. Proteinuria/albuminuria is not just a marker; but it also plays a direct pathogenic role in renal disease progression of CKD. Glomerular filtration barrier (GFB) which consists of fenestrated endothelial cells, fused basal membrane and interdigitating podocyte foot process and filtration slits between foot process is the major barrier for proteinuria/albuminuria. Many glomerular diseases are characterized by disruption of GFB podocytes, foot process and slit diaphragm. Many proteinuric diseases are non-specifically targeted by therapeutic agents such as steroids and calcineurin inhibitors with systemic side effects. Thus, there is unmet need for more efficient and less toxic therapeutic options to treat glomerular diseases. In recent years, modification of dietary intake, has been gained to treat pathologic processes introducing the concept of 'food as a medicine'. The effect of various nutritional products on podocyte function and structure is also trending, especially in recent years. In the current review, we summarized the effect of nutritional interventions on podocyte function and structure.

ESPEN guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease.

Acute kidney disease (AKD) - which includes acute kidney injury (AKI) - and chronic kidney disease (CKD) are highly prevalent among hospitalized patients, including those in nephrology and medicine wards, surgical wards, and intensive care units (ICU), and they have important metabolic and nutritional consequences. Moreover, in case kidney replacement therapy (KRT) is started, whatever is the modality used, the possible impact on nutritional profiles, substrate balance, and nutritional treatment processes cannot be neglected. The present guideline is aimed at providing evidence-based recommendations for clinical nutrition in hospitalized patients with AKD and CKD. Due to the significant heterogeneity of this patient population as well as the paucity of high-quality evidence data, the present guideline is to be intended as a basic framework of both evidence and - in most cases - expert opinions, aggregated in a structured consensus process, in order to update the two previous ESPEN Guidelines on Enteral (2006) and Parenteral (2009) Nutrition in Adult Renal Failure. Nutritional care for patients with stable CKD (i.e., controlled protein content diets/low protein diets with or without amino acid/ketoanalogue integration in outpatients up to CKD stages four and five), nutrition in kidney transplantation, and pediatric kidney disease will not be addressed in the present guideline.

Sum of skinfolds measurement can be used in the estimation of total body fat in patients with chronic kidney disease undergoing hemodialysis / La medición de la suma de los pliegues cutáneos puede utilizarse en la estimación de la grasa corporal total en los pacientes con nefropatía crónica sometidos a hemodiálisis

INTRODUCTION: body fat reflects important clinical impacts among hemodialysis patients; thus, simple and safe methods are required for a careful evaluation of this body compartment. OBJECTIVES: to evaluate the concordance of estimates of total body fat percentage (%BF), calculated using bioelectrical impedance analysis (BIA) and sum of four skinfolds (SSKD) measures, with those obtained using dual-energy X-ray absorptiometry (DEXA) in patients with chronic kidney disease (CKD) receiving hemodialysis. METHODS: a cross-sectional study was conducted in 317 patients undergoing hemodialysis. The %BF was evaluated using BIA, SSKD measurement, and DEXA, and stratified by sex and tertiles. The Wilcoxon test for paired samples was used to compare the %BF obtained using the different methods, and Lin's concordance correlation coefficient (CCC-L) to evaluate concordance. RESULTS: the average %BF estimated using DEXA was 29.3 ± 9.3 %, with significant differences among the three methods (p < 0.05). SSKD measurement presented a higher CCC-L concordance with DEXA, regardless of sex. After stratification of the sample in tertiles, BIA presented a higher CCC-L concordance with DEXA among the patients with CKD with a %BF above 34.4 % (third tertile). Conversely, SSKD measurement presented better concordance with DEXA for those with a %BF equal to or less than 34.4 %. CONCLUSIONS: in terms of the estimates of the %BF, SSKD measurement displayed a better concordance with DEXA

INTRODUCCIÓN: la grasa corporal refleja importantes impactos clínicos entre los pacientes en hemodiálisis; por lo tanto, se requieren métodos simples y seguros para una evaluación cuidadosa de este compartimiento del cuerpo. OBJETIVOS: evaluar la concordancia de las estimaciones del porcentaje de grasa corporal total (%GC), calculadas mediante el análisis de impedancia bioeléctrica (BIA) y la suma de las medidas de cuatro pliegues cutáneos (CPC), con las obtenidas mediante absorciometría dual energética de rayos X (DEXA) en pacientes con enfermedad renal crónica (ERC) que reciben hemodiálisis. MÉTODOS: se realizó un estudio transversal en 317 pacientes en hemodiálisis. La %GC se evaluó mediante BIA, medición de CPC y DEXA, y se estratificó por sexos y terciles. Se utilizó la prueba de Wilcoxon para muestras pareadas para comparar los %GC obtenidos con los diferentes métodos, y el coeficiente de correlación de concordancia de Lin (CCC-L) para evaluar la concordancia. RESULTADOS: el %GC promedio estimado usando DEXA fue del 29,3 ± 9,3 %, con diferencias significativas entre los tres métodos (p < 0,05). La medición de los CPC presentó una mayor concordancia de CCC-L con DEXA, independientemente del sexo. Tras la estratificación de la muestra en terciles, la BIA presentó una mayor concordancia de CCC-L con DEXA entre los pacientes con ERC con un %GC superior al 34,4 % (tercer tercil). Por el contrario, la medición de los CPC presentó una mejor concordancia con la DEXA para aquellos con un %GC igual o inferior al 34,4 %. CONCLUSIÓN: en términos de las estimaciones del %GC, la medición de los CPC mostró una mejor concordancia con la DEXA

Recipe Development for the Kidney Patient.

Kidney patients are restricted from sodium, potassium, phosphorus, and protein. In thisstudy, new recipes have been developed in order to prevent the decrease in appetite, to control the loss of liquid electrolytes due to vomiting, to help patients feel better by improving their morale, to facilitate their adaptation to the diet. Eight selected foods were prepared by modified for reducing sodium, potassium, and phosphorus (repeating 2 times) and by standard recipes (repeating two times). Eight foods and 16 recipes were obtained. Sodium, potassium, phosphorus, and protein contents were measured after the process. Sodium, potassium, and phosphorus contents were analyzed with the ICP-MS method. Protein content was analyzed with the Kjeldahl nitrogen determination method. Applied cooking methods led to a decrease in sodium, potassium, phosphorus, and protein levels in the modified foods. The highest loss rate (65.3%) was observed in proteins in apple halva. The lowest loss (21.5%) was determined in the potassium in the banana cake. These cooking methods can be useful for enriching the meals of kidney patients.

Oxidative stress mitigation by antioxidants - An overview on their chemistry and influences on health status.

The present review paper focuses on the chemistry of oxidative stress mitigation by antioxidants. Oxidative stress is understood as a lack of balance between the pro-oxidant and the antioxidant species. Reactive oxygen species in limited amounts are necessary for cell homeostasis and redox signaling. Excessive reactive oxygenated/nitrogenated species production, which counteracts the organism's defense systems, is known as oxidative stress. Sustained attack of endogenous and exogenous ROS results in conformational and oxidative alterations in key biomolecules. Chronic oxidative stress is associated with oxidative modifications occurring in key biomolecules: lipid peroxidation, protein carbonylation, carbonyl (aldehyde/ketone) adduct formation, nitration, sulfoxidation, DNA impairment such strand breaks or nucleobase oxidation. Oxidative stress is tightly linked to the development of cancer, diabetes, neurodegeneration, cardiovascular diseases, rheumatoid arthritis, kidney disease, eye disease. The deleterious action of reactive oxygenated species and their role in the onset and progression of pathologies are discussed. The results of oxidative attack become themselves sources of oxidative stress, becoming part of a vicious cycle that amplifies oxidative impairment. The term antioxidant refers to a compound that is able to impede or retard oxidation, acting at a lower concentration compared to that of the protected substrate. Antioxidant intervention against the radicalic lipid peroxidation can involve different mechanisms. Chain breaking antioxidants are called primary antioxidants, acting by scavenging radical species, converting them into more stable radicals or non-radical species. Secondary antioxidants quench singlet oxygen, decompose peroxides, chelate prooxidative metal ions, inhibit oxidative enzymes. Moreover, four reactivity-based lines of defense have been identified: preventative antioxidants, radical scavengers, repair antioxidants, and those relying on adaptation mechanisms. The specific mechanism of a series of endogenous and exogenous antioxidants in particular aspects of oxidative stress, is detailed. The final section resumes critical conclusions regarding antioxidant supplementation.

Methionine restriction delays senescence and suppresses the senescence-associated secretory phenotype in the kidney through endogenous hydrogen sulfide.

Aging is a risk factor for various acute and chronic kidney injuries. Kidney aging is accompanied by the secretion of growth factors, proteases, and inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). These factors accelerate the aging process and senescence-associated changes. Delaying kidney senescence may prevent acute and chronic kidney injury. Methionine restriction (MR) was found to be an effective intervention for delaying senescence. However, the mechanism of MR remains unclear. In this study, we investigated the effect of MR on the survival rate and renal aging of C57BL/6 mice and examined the relevant mechanisms. MR increased the survival rate and decreased the levels of senescence markers in the aging kidney. Both in vivo and in vitro, MR upregulated the transsulfuration pathway to increase H2S production, downregulated senescence markers and the SASP, and activated AMPK. The ability of MR to delay aging was reduced when AMPK was inhibited. These results suggest that MR may slow animal aging and kidney senescence through H2S production and AMPK pathway activation. Abbreviations: DR: diet restriction; MR: methionine restriction; SASP: senescence-associated secretory phenotype; AL: ad libitum; CKD, chronic kidney disease; AKI: acute kidney disease; TSP: transsulfuration pathway; CGL: cystathionine g-lyase; H2S: hydrogen sulfide; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; IS: indoxyl sulfate; CC: compound C.

Renal Diet.

Caring for a patient with renal disease requires an understanding of the basics renal nutritional therapy. The goals of nutritional therapy include maintaining renal function, preventing complications, and providing adequate nutrients. Because cardiovascular disease and hypertension are highly correlated with renal disease, sodium reduction is a major goal of the renal diet. Particularly in early stage renal disease, the Mediterranean diet and the dietary approaches to stop hypertension (DASH) eating plan may help to prevent disease progression. The role of other nutrients such as phosphorous, calcium, protein, and potassium will also be discussed.

Low protein diets for non-diabetic adults with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is defined as reduced function of the kidneys present for 3 months or longer with adverse implications for health and survival. For several decades low protein diets have been proposed for participants with CKD with the aim of slowing the progression to end-stage kidney disease (ESKD) and delaying the onset of renal replacement therapy. However the relative benefits and harms of dietary protein restriction for preventing progression of CKD have not been resolved. This is an update of a systematic review first published in 2000 and updated in 2006 and 2009. OBJECTIVES: To determine the efficacy of low protein diets in preventing the natural progression of CKD towards ESKD and in delaying the need for commencing dialysis treatment in non-diabetic adults. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 2 March 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi RCTs in which adults with non-diabetic chronic kidney disease (stages 3 to 5) not on dialysis were randomised to receive a very low protein intake (0.3 to 0.4 g/kg/d) compared with a low protein intake (0.5 to 0.6 g/kg/d) or a low protein intake compared with a normal protein intake (≥ 0.8 g/kg/d) for 12 months or more. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and extracted data. For dichotomous outcomes (death, all causes), requirement for dialysis, adverse effects) the risk ratios (RR) with 95% confidence intervals (CI) were calculated and summary statistics estimated using the random effects model. Where continuous scales of measurement were used (glomerular filtration rate (GFR), weight), these data were analysed as the mean difference (MD) or standardised mean difference (SMD) if different scales had been used. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: We identified an additional six studies to include 17 studies with 2996 analysed participants (range 19 to 840). Four larger multicentre studies were subdivided according to interventions so that the review included 21 separate data sets. Mean duration of participant follow-up ranged from 12 to 50 months.Random sequence generation and allocation concealment were considered at low risk of bias in eleven and nine studies respectively. All studies were considered at high risk for performance bias as they were open-label studies. We assessed detection bias for outcome assessment for GFR and ESKD separately. As GFR measurement was a laboratory outcome all studies were assessed at low risk of detection bias. For ESKD, nine studies were at low risk of detection bias as the need to commence dialysis was determined by personnel independent of the study investigators. Five studies were assessed at high risk of attrition bias with eleven studies at low risk. Ten studies were at high risk for reporting bias as they did not include data which could be included in a meta-analysis. Eight studies reported funding from government bodies while the remainder did not report on funding.Ten studies compared a low protein diet with a normal protein diet in participants with CKD categories 3a and b (9 studies) or 4 (one study). There was probably little or no difference in the numbers of participants who died (5 studies 1680 participants: RR 0.77, 95% CI 0.51 to 1.18; 13 fewer deaths per 1000; moderate certainty evidence). A low protein diet may make little or no difference in the number of participants who reached ESKD compared with a normal protein diet (6 studies, 1814 participants: RR 1.05, 95% CI 0.73 to 1.53; 7 more per 1000 reached ESKD; low certainty evidence). It remains uncertain whether a low protein diet compared with a normal protein intake impacts on the outcome of final or change in GFR (8 studies, 1680 participants: SMD -0.18, 95% CI -0.75 to 0.38; very low certainty evidence).Eight studies compared a very low protein diet with a low protein diet and two studies compared a very low protein diet with a normal protein diet. A very low protein intake compared with a low protein intake probably made little or no difference to death (6 studies, 681 participants: RR 1.26, 95% CI 0.62 to 2.54; 10 more deaths per 1000; moderate certainty evidence). However it probably reduces the number who reach ESKD (10 studies, 1010 participants: RR 0.65, 95% CI 0.49 to 0.85; 165 per 1000 fewer reached ESKD; moderate certainty evidence). It remains uncertain whether a very low protein diet compared with a low or normal protein intake influences the final or change in GFR (6 studies, 456 participants: SMD 0.12, 95% CI -0.27 to 0.52; very low certainty evidence).Final body weight was reported in only three studies. It is uncertain whether the intervention alters final body weight (3 studies, 89 participants: MD -0.40 kg, 95% CI -6.33 to 5.52; very low certainty evidence).Twelve studies reported no evidence of protein energy wasting (malnutrition) in their study participants while three studies reported small numbers of participants in each group with protein energy wasting. Most studies reported that adherence to diet was satisfactory. Quality of life was not formally assessed in any studies. AUTHORS' CONCLUSIONS: This review found that very low protein diets probably reduce the number of people with CKD 4 or 5, who progress to ESKD. In contrast low protein diets may make little difference to the number of people who progress to ESKD. Low or very low protein diets probably do not influence death. However there are limited data on adverse effects such as weight differences and protein energy wasting. There are no data on whether quality of life is impacted by difficulties in adhering to protein restriction. Studies evaluating the adverse effects and the impact on quality of life of dietary protein restriction are required before these dietary approaches can be recommended for widespread use.

Immunosuppressive and antiviral treatment of hepatitis C virus-associated glomerular disease: A long-term follow-up.

BACKGROUND: The evidence in the medical literature on the treatment of hepatitis C virus-associated glomerular disease is extremely limited. The advent of nonconventional immunosuppressive agents and direct-acting antivirals promises high efficacy and safety. AIMS: We conducted an open-label, single-arm clinical study to examine the efficacy and safety of a combined approach for hepatitis C virus-associated glomerular disease. METHODS: In the first phase of the study, patients with hepatitis C virus-associated glomerular disease received interferon-based antiviral therapy and immunosuppressive agents; since 2013, interferon-free antiviral therapy was adopted and novel immunosuppressants (including B-cell depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were choiced. Virological and clinical responses were evaluated over a long observation period (median follow-up of 60 weeks and 46.5 months after the end of treatment with interferon and direct-acting antiviral agents, respectively). RESULTS: We enrolled 25 consecutive patients with hepatitis C virus-associated glomerular disease, 8 being liver transplant recipients for hepatitis C. A total of 13 patients received therapy with direct-acting antivirals and experienced sustained viral response (serum hepatitis C virus RNA <12 IU/mL, 12 weeks after treatment ended, sustained viral response12). The mean (±standard deviation) proteinuria decreased from 2.61 ± 1.01 at baseline to 1.71 ± 1.43 (g/day) at sustained viral response 48, p = 0.031; microscopic hematuria and serum cryoglobulins disappeared in six (50%) and seven (64%) patients, respectively, after sustained viral response by direct-acting antivirals. Adverse events occurred in 69% (9/13) of patients and were mild, with four cases of ribavirin-related anemia requiring blood transfusions (no drop-outs). After sustained viral response by direct-acting antivirals, immunosuppressive and immunomodulatory agents were initiated in clinical relapsers ( n = 2) and nonresponders ( n = 3) with some benefit. Among patients on interferon-based regimens ( n = 12), viral response (sustained viral response 24) and dropout rates were 58% (7/12) and 33% (4/12), respectively. After sustained viral response by interferon-based therapy, clinical relapsers ( n = 3) were successfully managed with immunosuppressive agents in two patients. CONCLUSION: Treatment with direct-acting antivirals provides excellent rates of viral response and safety in patients with hepatitis C virus-related glomerular disease; viral response was frequently accompanied by clinical improvement. The absence of hepatitis C virus RNA from serum allowed immunosuppressive and immunomodulatory therapies with benefits for glomerular abnormalities and no concern on hepatitis C virus replication.

Systematic Review and Metaanalysis Comparing the Bias and Accuracy of the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration Equations in Community-Based Populations.

BACKGROUND: The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. CONTENT: MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1-3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6-3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. SUMMARY: Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR.