Fatty Kidney Research Articles

2250-PUB: Fatty Acid Composition and Diabetic Kidney Disease in Type 2 Diabetes

Aim: Elevated saturated fatty acid (SFA) and decreased polyunsaturated fatty acid (PUFA) levels, especially n-3 PUFAs levels are important in the development of obesity and metabolic syndrome, but there are few accounts of the relationship between fatty acid composition and diabetic kidney disease. We investigated whether serum fatty acid composition, especially SFA and PUFA, are associated with urine albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) in obese type 2 diabetic patients. Research Design and Method: The subjects were 85 patients (age: 60.3±13.9 years old, 47 male and 38 female) who were not taking EPA agents. They were divided into two groups, i.e., Obese group (n=54) with a BMI of more than 25 kg/m2 and non-Obese group (n=31) with a BMI below 25 kg/m2. Serum levels of fatty acids were measured by gas chromatography. Results: In the Obese group, the serum levels of palmitic acids and stearic acids, which belong to SFA, and dihomo-gamma-linolenic acid (DGLA), which is an n-6 PUFA, were significantly higher than those in the non-Obese group. No significant differences were seen in the serum levels of n-3 PUFA. UAE in the Obese group was 218.8±88.9 mg/gCr, which tended to be higher than that in the non-Obese group (135.9±49.0 mg/gCr), but there were no significant differences in eGFR between the two groups. The serum levels of palmitic acids, stearic acids, and DGLA showed significant positive correlations with UAE and eGFR in the Obese group, while no significant correlation was seen in the non-Obese group. Palmitic acids and DGLA were correlated with serum adiponectin and leptin levels. Conclusion: These results suggest that an excessive lipid intake may play an important role in the development of not only obesity but also diabetic kidney disease. The high levels of blood SFA and n-6 PUFA might contribute to the diabetic kidney disease progression via hyperfiltration and inflammatory effects in type 2 diabetes patients with obesity. Disclosure M. Kawai: None. R. Eto: None. F. Ayako: None. G. Sato: None. M. Hijikata: None. K. Yamashita: None. T. Ichijo: None. M. Higa: None.

1858-P: Bidirectional Relationship between Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus

Background: Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are highly prevalent in type 2 diabetes mellitus (T2DM). Growing evidence suggests that NAFLD and CKD share common traditional risk factors, but it would seem unique risk pathways are involved as a consequence of NAFLD and CKD, efforts are still needed for a more comprehensive understanding of these relationship. Methods: A structural equation model (SEM) was applied to assess associations between demographic data, inflammation factor, anthropometric and metabolic variables simultaneously and estimated glomerular filtration rate (eGFR) and fatty liver index (FLI). Given the potential that the NAFLD and CKD relationship may be bidirectional, SEMs also to examine direct and indirect effects of NAFLD on CKD, and vice versa. Results: A total of 1,992 subjects with T2DM were enrolled in this study. Using multivariate analysis, NAFLD was independently associated with the risk of CKD (adjusted OR=1.59, 95% CI=1.12-2.25, P=0.009). SEMs showed that age (-0.216), triglyceride (-0.129), uric acid (UA, -0.415), albumin (0.163), and HbA1c (-0.066) levels had direct effects on eGFR, and the final model could explain 30% of the variability in eGFR. Age (0.094), triglyceride (0.174), body mass index (BMI) (0.707), UA (0.092), white blood cell (WBC) count (0.070), serum glutamic pyruvic transaminase (0.132) levels, and smoking (0.066) status had direct effects on FLI, and the final model could explain 67% of the variability in FLI. The common risk factors contributed to both eGFR and FLI were age, triglyceride, and UA. Unique risk factors were albumin and HbA1c for eGFR, and BMI, WBC, SGPT, and smoking for FLI. SEMs analysis confirm the bidirectional cause-relationships between NAFLD and CKD. Conclusions: Common and unique risk factors and bidirectional relationship exist between CKD and NAFLD in patients with T2DM. Disclosure H. Hsu: None. Y. Chang: None. L. An: None. T. Lee: None.

1 H-MRS for the assessment of renal triglyceride content in humans at 3T: A primer and reproducibility study.

Renal steatosis (fatty kidney) is a potential biomarker for obesity-related renal disease; however, noninvasive assessment of renal fat content remains a technical challenge. To evaluate reproducibility and explore clinical application of renal metabolic imaging for the quantification of renal triglyceride content (TG) using proton magnetic resonance spectroscopy (1 H-MRS). Reproducibility and clinical cohort study. Twenty-three healthy volunteers (mean age 30.1 ± 13.4 years) and 15 patients with type 2 diabetes mellitus (T2DM) (mean age 59.3 ± 7.0 years). 3T, single-voxel point resolved spectroscopy (PRESS). Intra- and interexamination reproducibility of renal TG was assessed in healthy volunteers, and compared to T2DM patients. Intraexamination differences were obtained by repeating the 1 H-MRS measurement directly after the first 1 H-MRS without repositioning of the subject or changing surface coil and measurement volumes. Interexamination variability was studied by repeating the scan protocol after removal and replacement of the subject in the magnet, and subsequent repositioning of body coil and measurement volumes. Reproducibility was determined using Pearson's correlation and Bland-Altman analyses. Differences in TG% between healthy volunteers and T2DM patients were assessed using the Mann-Whitney U-test. After logarithmic (log) transformation, both intraexamination (r = 0.91, n = 19) and interexamination (r = 0.73, n = 9) measurements of renal TG content were highly correlated with the first renal TG measurements. Intraexamination and interexamination limits of agreement of renal log TG% were respectively [-1.36%, + 0.84%] and [-0.77%, + 0.62%]. Backtransformed limits of agreement were [-0.89%,+0.57%] and [-0.55%, + 0.43%] multiplied by mean TG for intra- and interexamination measurements. Overall median renal TG content was 0.12% [0.08, 0.22; 25th percentile, 75th percentile] in healthy volunteers and 0.20% [0.13, 0.22] in T2DM patients (P = 0.08). Renal metabolic imaging using 3T 1 H-MRS is a reproducible technique for the assessment of renal triglyceride content. 3 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:507-513.

Metabolic imaging of fatty kidney in diabesity: validation and dietary intervention.

Obesity and type 2 diabetes have not only been linked to fatty liver, but also to fatty kidney and chronic kidney disease. Since non-invasive tools are lacking to study fatty kidney in clinical studies, we explored agreement between proton magnetic resonance spectroscopy (1H-MRS) and enzymatic assessment of renal triglyceride content (without and with dietary intervention). We further studied the correlation between fatty kidney and fatty liver. Triglyceride content in the renal cortex was measured by 1H-MRS on a 7-Tesla scanner in 27 pigs, among which 15 minipigs had been randomized to a 7-month control diet, cafeteria diet (CAF) or CAF with low-dose streptozocin (CAF-S) to induce insulin-independent diabetes. Renal biopsies were taken from corresponding MRS-voxel locations. Additionally, liver biopsies were taken and triglyceride content in all biopsies was measured by enzymatic assay. Renal triglyceride content measured by 1H-MRS and enzymatic assay correlated positively (r = 0.86, P < 0.0001). Compared with control diet-fed minipigs, renal triglyceride content was higher in CAF-S-fed minipigs (137 ± 51 nmol/mg protein, mean ± standard error of the mean, P < 0.05), but not in CAF-fed minipigs (60 ± 10 nmol/mg protein) compared with controls (40 ± 6 nmol/mg protein). Triglyceride contents in liver and kidney biopsies were strongly correlated (r = 0.97, P < 0.001). Non-invasive measurement of renal triglyceride content by 1H-MRS closely predicts triglyceride content as measured enzymatically in biopsies, and fatty kidney appears to develop parallel to fatty liver. 1H-MRS may be a valuable tool to explore the role of fatty kidney in obesity and type 2 diabetic nephropathy in humans in vivo.

Urine liver fatty acid binding protein and chronic kidney disease progression

Excretion of the tubular protein liver fatty acid binding protein (L-FABP) is a potential novel biomarker of renal dysfunction. We examined whether urine L-FABP excretion adds prognostic information to the well-established risk markers, blood pressure (BP), albumin excretion and baseline GFR, regarding progression of chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage 3-4 CKD patients (age 61 ± 13 years) were included. Glomerular filtration ratio (GFR, 51Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary albumin/creatinine ratio (UAC) and urinary L-FABP/creatinine ratio (U-L-FABP/C) were determined at baseline and after 18 months of follow-up. For comparison 25 age-matched healthy controls were included. The U-L-FABP/C was elevated in CKD patients when compared to controls (mean U-L-FABP/C 2.3 [95% CI 1.7–2.9] μg/mmol vs 0.6 [0.5–0.7] μg/mmol, p < .001). In CKD patients, log U-L-FABP/C at baseline and at follow-up were positively associated (Pearson correlation coefficient r = 0.74, p < .001). Baseline log U-L-FABP/C was negatively correlated with baseline GFR (r = −0.32, p < .001) and directly correlated with UAC (r = 0.67, p < .001). The relative change in GFR from baseline to follow-up correlated with baseline UAC (p < .001), 24-hour systolic BP (p = 0.05) and log U-L-FABP/C (p < .001). Using multiple regression analysis adjusting for baseline GFR, UAC, BP, age and gender, baseline log U-L-FABP/C was associated with a decline in GFR only in patients with UAC <3 mg/mmol (n = 29, p = 0.001) and not in patients with UAC ≥3 mg/mmol (n = 44, p = 0.21). In conclusion urine L-FABP/C is permanently elevated in CKD patients, but only associated with GFR decline in those without albuminuria.

Fatty liver kidney syndrome (FLKS) in peafowl chicks (Pavo cristatus) and its management

Fatty liver kidney syndrome (FLKS) in peafowl chicks (<i>Pavo cristatus</i>) and its management

Obesity-related glomerulopathy: Mechanisms of development, clinical course

Obesity and overweight are recognized as epidemics of non-communicable diseases in the 21st century. The kidneys are a target organ for obesity, damage to which is considered to be an independent risk factor for the development of renal failure. Obesity-related glomerulopathy (OGP) is one of the types of renal injury in obesity, which is characterized by the development of proteinuria in patients with a body mass index (BMI) of >30 kg/m2 in the absence of other causes of kidney damage. The pathogenesis of OGP is multifactorial. It is associated with intrarenal hemodynamic disorders - the development of renal hyperfiltration, the damaging action of adipose tissue hormones (hyperleptinemia, activation of the renin-angiotensin-aldosterone system, decreased production of adiponectin); with ectopic lipid accumulation in the kidney. The morphological pattern of OGP is characterized by a low glomerular density (oligonephronia) that leads to glomerular and tubular hypertrophy; by the development of perihilar focal segmental glomerulosclerosis (FSGS), obvious podocyte damages, and the development of a fatty kidney. The clinical picture of OGP is characterized by the slow and gradual development of albuminuria, not exceeding Stage A3 (300-1999 mg/day). Approximately one-third of patients develop partial nephrotic syndrome with massive proteinuria, but without edema and hypoproteinemia. Complete nephrotic syndrome is observed in not more than 6% of patients with OGP. In the course of the disease, 50% of patients develop hypertension and more than 80% do dyslipidemia. Stages IV-V chronic kidney disease may develop 20-30 years after the disease occurs.

Multiple Roles of Curcumin Attenuate High Fat Diet- Induced Kidney Cortex Derangement

The urgency to develop renoprotective strategies sets the eyes in compounds as curcumin which prevents high fat diet-induced lipid accumulation and improves lipid profile in clinical studies. The present work aims to investigate the effect of curcumin on experimental nonalcoholic pattern kidney disease via histopathological, histochemical and immunohistochemical studies. Sixty Wister male rats weighing approximately 100 -120 grams were divided into 4 groups. Group I: 10 rats were served as control group and group II: 50 rats were received high fat diet for 12 weeks. Post histopathological confirmation of fatty kidney, this second group was subdivided into the following groups: Group III: 20 rats were injected intraperitoneally (I.P) with 1 /kg body weight dimethylsulfoxide (DMSO) day after day for 8 weeks. Group IV: 20 rats were injected I.P with 50 mg /kg body weight curcumin dissolved in DMSO, day after day for 8 weeks. The rest 10 rats in group II were sacrificed after 12 weeks from the beginning of experiment .Our histopathological results showed that renal structures of rats fed a high fat diet for 12 weeks had a dilatation in blood vessels and Bowman's space, mono nuclear cell infiltration, degeneration in nephrons and tubular defects. On the other hand rats treated with curcumin had nearly normal morphology of the kidney. Histochemical & immunohistochemical results showed decreased catalase (CAT) activity (96.08 ± 2.74) and decreased nuclear factor-kappa B (122.82 ± 5.44), endothelial nitric oxide synthase (eNOS) (128.23 ± 2.37) and inducible nitric oxide synthase (iNOS) (75.97 ± 6.29) in fatty rats improved after using curcumin (124.55 ± 18.82), (135.69 ± 6.39), (156.23 ± 4.94) and (95.39 ± 4.21) respectively. In conclusion, curcumin attenuates high fat diet induced kidney cortex derangement.

Fatty kidney diagnosed by mortem computed tomography

Subnuclear vacuolization of the renal tubular epithelium is indicative of diabetic and alcoholic ketoacidosis and has also been proposed as a postmortem marker for hypothermia. We present for the first time a fatal case of ketoacidosis in combination with exposure where a suspicion of these diagnoses was raised by a marked radiolucency of the kidneys at post-mortem computed tomography (PMCT).

Determination of Ethylenediaminetetraacetic Acid from Swine Organs, Feces, Urine, and Plasma by Liquid Chromatography Tandem Mass Spectrometry

The study describes the development of a method for determination of ethylenediaminetetraacetic acid (EDTA) in various biological matrices after extraction as sample preparation using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The method is based on the complex formation of the excess of EDTA with FeIII. The excretion of EDTA in swine, treated with high doses of EDTA against dysentery, was monitored over a week by measuring its concentration in urine, plasma, and feces after stopping the administration of the medication. After slaughter, the EDTA concentration was measured also in the fatty tissue, kidney, liver, and muscle in order to determine the distribution of its residue between the tissues. The new method is fast, and the one-step sample preparation procedure may be regarded as derivatization. The method is applicable for low-concentration analysis with 3.0 ng mL−1 limit of detection and 10.0 ng mL−1 limit of quantification, while the relative standard deviation does not exceed 4.3 %.

Does diagnosing fatty liver and chronic kidney disease do more good than harm?

In this week’s issue of PLOS Medicine, Musso and colleagues report that two conditions, both occupying increasing amounts of medical attention, may be linked [1]. Their paper demonstrates that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD) even after adjustment for major shared risk factors. ‘‘Future research,’’ they write, ‘‘should evaluate strategies and interventions to prevent renal disease

Fatty Kidney, Hypertension, and Chronic Kidney Disease

Ectopic fat depots may mediate local and systemic disease. Animal models of diet-induced obesity demonstrate increased fat accumulation in the renal sinus. The association of renal sinus fat with hypertension, chronic kidney disease, and other metabolic disorders has not been studied in a large, community-based sample. Participants from the Framingham Heart Study (n=2923; mean age: 54 years; 51% women) underwent quantification of renal sinus fat area using computed tomography. High renal sinus fat ("fatty kidney") was defined using sex-specific 90th percentiles in a healthy referent subsample. Multivariable linear and logistic regression was used to model metabolic risk factors as a function of fatty kidney and log-transformed renal sinus fat. Multivariable models were adjusted for age, sex, and outcome-specific covariates and then additionally adjusted for body mass index or abdominal visceral adipose tissue. The prevalence of fatty kidney was 30.1% (n=879). Individuals with fatty kidney had a higher odds ratio (OR) of hypertension (OR: 2.12; P<0.0001), which persisted after adjustment for body mass index (OR: 1.49; P<0.0001) or visceral adipose tissue (OR: 1.24; P=0.049). Fatty kidney was also associated with an increased OR for chronic kidney disease (OR: 2.30; P=0.005), even after additionally adjusting for body mass index (OR: 1.86; P=0.04) or visceral adipose tissue (OR: 1.86; P=0.05). We observed no association between fatty kidney and diabetes mellitus after adjusting for visceral adipose tissue. In conclusion, fatty kidney is a common condition that is associated with an increased risk of hypertension and chronic kidney disease. Renal sinus fat may play a role in blood pressure regulation and chronic kidney disease.

Fat Chance for Hypertension and Chronic Kidney Disease

See related article, pp 784–790 Obesity is firmly associated with both hypertension and chronic kidney disease (CKD). Although these areas have been the subject of intense investigation over the last 2 decades, the mechanisms and best clinical indicators are not fully resolved. In the current issue, Foster et al1 provide intriguing evidence associating increased renal sinus fat (“fatty kidney”) specifically with increased prevalence of hypertension and CKD. The prevalence of obesity continues to increase globally, as has occurred over the last few decades. Obesity has been definitively linked to hypertension and other cardiovascular diseases for many years. Numerous animal models and human studies have explored the mechanisms linking obesity to hypertension. Several factors have been consistently shown with obesity (Figure): increased sympathetic nervous system activity, increased renin-angiotensin-aldosterone system activity, and increased sodium reabsorption (and/or impaired pressure natriuresis) among other mechanisms.2,3 A variety of adipocyte-derived factors, such as leptin, have also been shown to be involved. In addition, local or systemic inflammatory cascades, endothelial dysfunction, and reactive oxygen species likely have a role in the mechanistic links between obesity and hypertension. Figure. Speculative diagram of the relationships between aspects of obesity, hypertension (HTN), and chronic kidney disease (CKD). Generalized obesity, abdominal (or visceral) obesity, and fatty kidney largely overlap but may have distinct mechanistic links …

IgA Nephropathy: Progress Before and Since Berger

Immunoglobulin A nephropathy (IgAN) is linked inextricably to the name Jean Berger, the Parisian pathologist who published the first description of IgAN in 1968. We reflect on the significance of Berger's first report and consider 40 years of progress in our understanding of IgAN since it was published. We also look back to the days before Berger, when IgAN could not have been identified (because there were no techniques for detecting IgA deposits), classification of glomerulonephritis was even more contentious and confusing than it is today, and it is likely that the literature describing focal glomerulonephritis contained many of the cases we would now identify as IgAN.

The histological demonstration of lipids in the proximal renal tubules of patients with diabetic coma.

The Armanni-Ebstein phenomenon is a vacuolization of the cells of the proximal kidney tubules in diabetic coma. It has been believed to represent glycogen. In the present examination of 14 cases of diabetic coma, high contents of lipids, probably triglycerides, were demonstrated in the vacuoles by histological staining. Only weak positive reactions were found in diabetic controls. In both alcoholic and nonalcoholic-nondiabetics, no lipid was found. The sensivity was very high, but it was difficult from the present material to ascertain the level of specificity. The authors suggest the term fatty kidney in diabetics.

Dietary Fatty Acids and Kidney Transplantation in the Rat

In five groups of 15 rats allogeneic kidney transplantations were performed. Four groups received pre- and postoperatively a semisynthetic diet, isocalorically but differing in quantity and quality of fatty acids: group I received a diet high in saturated fat; group II, a diet high in linoleic acid; group III, a diet containing fish oil; group IV, a diet high in monoenoic acid. Finally, the fifth group of rats was fed a standard commercial chow and served as a control for the procedure of technique and immunological regimen. All groups received the same immunosuppressive regimen of immunological enhancement induced by pretreatment with complete donor blood. Survival and several parameters of graft function were studied. The results showed that the technical mortality, i.e. animals dying in the first week after transplantation, was substantially higher in rats on the semisynthetic diets in comparison with the group of rats on the commercial diet. A statistically significant better graft function could be observed in the group of rats on the diet high in linoleic acid in the first period after kidney transplantation, compared to the other groups on semisynthetic diets. This difference disappeared in the course of the study when a number of animals was lost due to graft rejection. Furthermore, in the same diet group mortality due to rejection was significantly decreased as well.

The duck fatty kidney syndrome — An aspect of duck viral hepatitis

The duck fatty kidney syndrome accounted for mortalities of up to 30% on certain duck rearing farms in Britain from 1978 to 1983 and affected two distinct age groups of 1 to 2 and 4 to 6 weeks of age. Post mortem examinations revealed pale swollen kidneys and swollen mottled spleens. Histological examination of tissues suggested mild duck viral hepatitis, even though the birds were vaccinated against duck hepatitis virus type I and the older group was beyond the age at which age immunity to that disease usually develops. Studies on the pathogenesis of duck viral hepatitis suggested that the duck fatty kidney syndrome was a manifestation of that disease.

Fatty liver and kidney syndrome in chickens as an animal model for Reye's syndrome.

Fatty liver and kidney syndrome (FLKS), a naturally occurring but experimentally reproducible disease in chickens, has several clinical, pathological, and biochemical features in common with Reye's syndrome. Because of this, it has been suggested that FLKS may serve as an animal model of Reye's syndrome. We have examined, therefore, various parameters characteristic of Reye's syndrome in chickens affected with FLKS to further delineate the similarities and differences between the two disorders. Plasma glucose concentrations were significantly lower in chickens affected with FLKS which may be caused by the significantly reduced activity of pyruvate carboxylase in all FLKS-affected animals. The activity of propionyl CoA carboxylase was low in only the most severely affected chickens, and beta-methylcrotonyl CoA carboxylase showed no difference when compared with controls. This may be due to variable sensitivities of the three carboxylases to marginal biotin deficiency which occurs with FLKS. Plasma ammonia concentrations and activities of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, however, were not elevated in the affected birds. Histological changes in the liver and kidney were noted in affected chickens, but these changes were not identical with those observed in Reye's syndrome. Although the mechanisms of nitrogen elimination in fowl differ from those in humans, failure to demonstrate hyperammonemia, elevated serum transaminase activities, or similar histological changes in tissues of affected birds indicates that FLKS is not an appropriate model for the study of Reye's syndrome.

Incorporation of 3H-oleic acid by the proximal convoluted tubule cells of the chick (Gallus domesticus)

Lipid metabolism in the cells of the renal proximal convoluted tubules (PCT) was investigated in healthy fowls and in fowls with the Fatty Liver and Kidney Syndrome (FLKS). The tissue was fixed at 10-25 min intervals after intravenous injection of 3H-oleic acid. The distribution of autoradiographic grains was analysed by the "circle method". In normal cells most of the silver grains were associated with the cytoplasmic organelles. Lipid droplets and Golgi elements had the highest specific activity relative to the nuclear activity, which was little above background level. Lysosome-like bodies and mitochondria had lower values. In the cells of the FLKS-affected birds a large porportion of the grains was located over the lipid droplets, which are abundant in this condition. The specific activity of the cytoplasmic organelles was barely 2-fold higher than the nuclear activity. The results suggest that there is a diminished incorporation of esterified fatty acids by the organelles of these cells and that the excess is transferred to the lipid droplets. The identity of low electron density particles observed in the PCT cell of severely affected birds is discussed.

Cholesterol fatty kidney: Morphological changes in the course of its development in rabbits

Kidneys from 90 rabbits were examined by light microscopy after an experiment designed to assess the possible relation between the cholesterol content of various tissues and two other factors: the serum cholesterol level and duration of hypercholesteremia. An additional eight rabbits were fed a 2% cholesterol diet for various periods up to 90 days. These kidney tissues were examined under electron microscope after aldehyde fixation with 0.2% digitonin. Digitonin-induced laminar and microtubular structures appeared in the capillary lumen and endothelia 5 hr after cholesterol feeding. Subsequently, similar structures appeared in the glomerular visceral epithelia and tubular epithelia. Fat vacuoles were usually not observed by light microscopy because of their small size and number. The interstitial cells in the medulla were sensitive to hypercholesteremia and were transformed into foam cells. As these grew in number, fatty streaks appeared and extended from the subcortical zone toward pyramidal papilla. The glomerular mesangial cells also took up cholesterol, but only after prolonged exposure to extreme hyperlipidemia, they formed glomerular micro-xanthomas.