Impact of diet modification on body mass and kidney function in patients with diabetic nephropathy: a pilot study.

OBJECTIVES: The increasing trend in chronic kidney disease (CKD) has occurred in parallel with the increased prevalence of obesity and diabetes type 2. The relationship between a reduction in body mass and protein intake in diabetic nephropathy (DN) has not been adequately understood. This study aimed to determine whether dietary intervention in an adult with DN is associated with decreasing proteinuria or changes in kidney function over six months. METHODS: The study included 120 patients with DN, consecutively admitted to a dietitian from a Kidney Disease Clinic. Patients were classified into two groups: a reduction diet or a normal calorie diet, both with 0.8 g of protein/kg of ideal body weight/day. Anthropometric and laboratory assessments were done before and after observation. RESULTS: After six months, in the study group of patients on a reducing diet, a decrease in body mass, body mass index (BMI) and stabilization of estimated glomerular filtration rate (eGFR) were observed. There was also a significant correlation between the time of diabetes diagnosis and eGFR and creatinine (R Spearman=-0.24 and 0.3, respectively; p=0.05). There were no other significant associations between body mass, BMI, albuminuria, eGFR, or creatinine. CONCLUSIONS: The study shows that obesity is a common comorbid disease in patients with DN and that dietary intervention is associated with a significant reduction in body mass and stabilization of eGFR in these patients.

Associations between Serum Saturated Fatty Acids Content and Mortality in Dialysis Patients.

Background: Cardiovascular mortality in dialysis population remains very high. Saturated fatty acids (SFA) contribute to atherosclerosis and to cardiovascular risk. Aim: The aim of this study was to evaluate the relationship between mortality in dialysis patients and the serum SFA content. Methods: Survival of 54 patients on dialysis was assessed. A total of 21 SFA from patients' sera were measured by gas chromatography-mass spectrometry (GC-MS). Diet was assessed by food frequency questionnaire FFQ-6. The SFA content is presented as fatty acid proportion (%). Results: During the observation time (median 66 months) 22 patients died. There was a significant relationship between elevated SFA (above SFA mean) and mortality (log-rank 3.13; p = 0.0017). Moreover, patients who ingested foods rich in SFA, according to FFQ-6, had a higher mortality risk (log-rank 2.24; p = 0.03). The hazard ratio for mortality associated with increased SFA content equalled 4.47 (1.63−12.26). Addition of age and inflammation (hsCRP > 5 mg/L) into the Cox model did not modify this relationship. However, SFA content turned out to be significantly higher in patients with diabetes mellitus and cardiovascular disease, as compared to patients free from these co-morbidities. Their addition to the model attenuated the relationship between SFA and mortality, making it statistically insignificant. Conclusion: The serum content of SFA turned out to be a strong predictor of mortality in dialysis patients. However, given the significant associations between SFA, DM, and CVD, interventional studies with controlled SFA intake are needed to evaluate the causal links between SFA, co-morbidities and survival.

Recurrence of Cryoglobulinemia Secondary to Hepatitis C in a Patient with HCV RNA (-) Negative in the Serum.

Hepatitis C virus infection is associated with many extrahepatic manifestations such as mixed cryoglobulinemia (MC). Renal manifestation of HCV infection might present as cryo-positive membranoproliferative glomerulonephritis (MPGN). First-line therapy includes antiviral treatment as the underlying infection leads to formation of immune complexes. After introducing direct-acting antiviral agents (DAAs) cure rates of HCV infection increased. Sustained virologic response (SVR) is defined as the absence of HCV RNA in serum by a sensitive test performed 12 or 24 weeks after the end of antiviral treatment. Although HCV RNA is undetectable in the serum, it may be present in hepatocytes and peripheral blood mononuclear cells (occult HCV infection). However, the impact of DAA treatment on occult HCV infection is not clear. We report a case of recurrence of MC with MPGN and development of lymphoproliferative disorder 2 years after achieving SVR.

Disorders of Serum Polyunsaturated Fatty Acids in Renal Transplant Patients.

BACKGROUND: Disturbances in polyunsaturated fatty acids (PUFA) could predispose renal transplant (RTx) patients to cardiovascular risk. The purpose of this study was to evaluate serum content of ω-3 and ω-6 PUFA in RTx subjects, in comparison to nontransplanted chronic kidney disease (CKD) patients in predialysis stages and to healthy controls. In the second part of the study, PUFA were analyzed in subcutaneous adipose tissue of CKD subjects at the time of kidney transplantation. METHODS: The first part of the study was conducted in a cohort (n = 134) of 3 groups: patients after renal transplantation (RTx group, n = 24), patients with CKD in stages 2-5, not on dialysis (CKD-ND group, n = 67), and controls without CKD (control group, n = 43). The fatty acids (FA) assessed by gas chromatography-mass spectrometry (GC-MS) were alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA), and arachidonic acid (AA). Diet was assessed by food frequency questionnaire FFQ-6. In the second part of the study, the same FA were evaluated in samples of adipose tissue taken during the kidney transplantation procedure and compared with FA of controls from the adipose tissue collected during hernia surgeries. RESULTS: The first part of the study showed that RTx patients presented significantly lower serum content of all the examined PUFA, in comparison to the CKD-ND group and controls. For instance, EPA in RTx equaled 0.65 ± 0.32%, in CKD-ND 0.82 ± 0.43%, and in controls 1.06 ± 0.68% (P = .005). No significant correlations were found between serum PUFA and diet in RTx patients. The second part of the study revealed no significant difference in the adipose tissue PUFA between CKD patients at the time of kidney transplantation and controls. CONCLUSIONS: RTx patients present with low serum content of potentially beneficial PUFA. This finding does not seem to be solely due to an altered diet. Observed disorders might result from immunosuppressive drugs or other, yet undetermined, causes.

Alterations of Fatty Acid Profile May Contribute to Dyslipidemia in Chronic Kidney Disease by Influencing Hepatocyte Metabolism.

Chronic kidney disease (CKD) is associated with atherogenic dyslipidemia. Our aim was firstly to investigate patterns of fatty acids (FA) composition through various stages of CKD, and secondly, to evaluate the effect of CKD-specific FA disturbances on the expression of genes related to lipid metabolism at a cellular level. Serum FA composition was analyzed in 191 patients with consecutive severity stages of CKD, and 30 healthy controls free from CKD. Next, HepG2 human hepatic cells were treated with major representatives of various FA groups, as well as with FA extracted from a mix of serums of controls and of CKD stage 5 patients. Across worsening stages of CKD severity, there was an increasing monounsaturated FA (MUFA) content. It was associated with a concomitant decrease in n-3 and n-6 polyunsaturated FA. The incubation of hepatocytes with FA from CKD patients (compared to that of healthy subjects), resulted in significantly higher mRNA levels of genes involved in FA synthesis (fatty acid synthase (FASN) increased 13.7 ± 3.5 times, stearoyl-CoA desaturase 1 (SCD1) increased 4.26 ± 0.36 times), and very low density lipoprotein (VLDL) formation (apolipoprotein B (ApoB) increased 7.35 ± 1.5 times, microsomal triacylglycerol transfer protein (MTTP) increased 2.74 ± 0.43 times). In conclusion, there were progressive alterations in serum FA composition of patients with CKD. These alterations may partly contribute to CKD hypertriglyceridemia by influencing hepatocyte expression of genes of lipid synthesis and release.

Multiplatform metabolomics provides insight into the molecular basis of chronic kidney disease.

Changes in metabolites composition can reflect currently present pathological processes in a living organism and constitute a basis for diagnosis and treatment improvements. Thus, the multiplatform metabolomics approach was applied for the investigation of molecular mechanisms of chronic kidney disease (CKD) progression. The high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF-MS) and gas chromatography coupled with triple quadrupole mass spectrometry (GC-QqQ/MS) serum metabolic fingerprinting followed by uni- and multivariate statistical analysis was carried out to determine metabolic pattern differentiating CKD patients and healthy controls. Furthermore, metabolites changes between stage 3 and 4 of the disease, as well as health status were investigated. The progression of the disease was found to be related to alterations in acylcarnitine, amino acid, lysophospholipid and carbohydrate metabolism. Elevated levels of serum acylcarnitines, sugar alcohols, and organic acids, as well as decreased levels of lysophospholipids, and amino acids, were found to be statistically significant for CKD progression. The obtained results confirm the utility of metabolomics approach as a tool for an explanation of molecular processes underlying CKD development.

Potential contribution of monounsaturated fatty acids to cardiovascular risk in chronic kidney disease.

INTRODUCTION Patients with chronic kidney disease (CKD) are particularly susceptible to cardiovascular disease (CVD). Increased synthesis of endogenous monounsaturated fatty acids (MUFAs) by stearoyl-CoA desaturase-1 (SCD1) might predispose to cardiovascular complications. OBJECTIVES The aim of this study was to examine the serum MUFA content in patients at subsequent stages of CKD, and to evaluate associations between MUFA content and SCD1 activity, patients' diet, and cardiovascular risk. PATIENTS AND METHODS Serum fatty acid composition was evaluated in 177 patients with subsequent stages of CKD (1-2, 3a, 3b, 4-5, hemodialysis, peritoneal dialysis, and after kidney transplantation), and in 30 healthy controls. Gas chromatography-mass spectrometry was used for the measurement. RESULTS Serum MUFA content was shown to increase with subsequent stages of CKD and to be correlated with various risk factors of CVD, including serum triacylglycerols, HDL cholesterol (P <0.01), and high-sensitivity C-reactive protein (P <0.05). Moreover, also the prevalence of CVD was shown to increase with CKD progression. Estimated SCD1 activity was associated with serum MUFA content (P <0.01), but no association was found between dietary MUFA intake and serum MUFA levels. CONCLUSIONS Our results indicate that the elevation of serum MUFA levels in CKD patients may contribute to an increased risk of CVD during CKD progression, mainly due to increased endogenous MUFA synthesis by SCD1.

Disorders of serum omega-3 fatty acid composition in dialyzed patients, and their associations with fat mass.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular mortality. Lipid disorders, a constant feature of CKD, might contribute to this state. The aim of this study was to evaluate n-3 polyunsaturated fatty acids (PUFA) composition in CKD patients treated with dialysis, in comparison to the general population and to assess possible associations between the n-3 PUFA profile and anthropometric variables. Thirty-three prevalent dialysis patients were studied and compared with an age- and sex-adjusted control group of 22 patients. Fatty acid composition in serum was analyzed by gas chromatography with a mass spectrometer detector (GC-MS) and anthropometric measures were assessed by bioimpedance spectroscopy. The fatty acid profile of dialyzed patients was characterized by a significantly lower percentage content of n-3 PUFA. For α-linolenic acid (ALA), it was 0.21 ± 0.09% in dialysis patients versus 0.33 ± 0.11% in the control group (p < .001). For eicosapentanoic acid (EPA), 0.59 ± 0.23% versus 1.15 ± 0.87% (p < .001), and for docosahexaenoic acid (DHA) 1.11 ± 0.50% versus 1.75 ± 0.87% (p < .001), respectively. The amount of n-3 PUFA decreased with time on dialysis and it correlated positively with body fat mass. For DHA, this correlation was r = .48 (p < .01) and for EPA r = .40 (p < .05). Patients with CKD have a relatively low content of n-3 PUFA which may contribute to their high cardiovascular risk. Patients with a higher content of body fat are characterized by a favorable fatty acid composition.

Impact of gender and dialysis adequacy on anaemia in peritoneal dialysis.

PURPOSE: In the general population, haemoglobin (Hb) concentration is higher in men than in women. However, target Hb levels in dialysis patients are set constant regardless of the patient's sex. The aim of this study was to evaluate Hb concentration and the use of erythropoiesis-stimulating agents (ESA) in peritoneal dialysis (PD) patients taking gender and dialysis adequacy into account. METHODS: The study comprised two parts. The first was a cross-sectional analysis of Hb and ESA in 2180 prevalent PD patients. The second included 88 incident PD patients, followed for 36 months. During this time, the major parameters recorded at 12-month intervals included: Hb concentration, weekly ESA, total, renal, and peritoneal Kt/V. Erythropoietin resistance index (ERI) was calculated as the ratio between ESA dose and achieved Hb. RESULTS: In prevalent PD patients, Hb concentration was significantly lower in women, (11.2 ± 1.4 vs. 11.5 ± 1.6 g/dl; p < 0.001), despite higher doses of ESA (2691 ± 1821 vs. 2344 ± 1422; p = 0.001). Hb concentrations were related to dialysis adequacy in both cohorts. However, despite significantly higher Kt/V, women were characterized by a lower Hb level. In incident patients, this association was present throughout the observation period, while the ESA dose in women was significantly higher at every time point. In multiple regression analysis, gender was an independent determinant of ERI (b = 0.34; p < 0.05). CONCLUSIONS: Despite higher dialysis adequacy, Hb concentration in women treated with PD is significantly lower, and the ability to correct it impaired, as compared to men.