Andrzej Brymora

Low-fructose diet lowers blood pressure and inflammation in patients with chronic kidney disease

BACKGROUND Fructose has been strongly linked with hypertension, hyperuricemia and inflammation in experimental models and humans. However, the effect of low-fructose diet on inflammation, hyperuricemia and the progression of renal disease has not yet been evaluated in patients with chronic kidney disease (CKD). METHODS Twenty-eight patients (age 59 ± 15 years, 17 males/11 females) with Stages 2 and 3 CKD were switched from a regular (basal) (60.0 g/24 h) to a low (12.0 g/24 h) fructose diet for 6 weeks, followed by a resumption of their regular diet for another 6 weeks. Diet was monitored by a dietician. At the baseline, low- and regular-fructose diet ambulatory blood pressure (BP) was measured and blood sampled for renal function (creatinine), inflammatory markers, fasting glucose and insulin and serum uric acid. Twenty-four-hour urine collections were also obtained for creatinine, uric acid, monocyte chemotatic protein-1, transforming growth factor-beta and N-acetyl-beta-D-glucosaminidase. RESULTS The low-fructose diet tended to improve BP for the whole group (n = 28), while significant reduction of BP was only seen in dippers (n = 20) but not in non-dippers (n = 8). No effects on estimated glomerular filtration rate (eGFR) or proteinuria were observed. Serum uric acid was lowered non-significantly with low-fructose diet (7.1 ± 1.3 versus 6.6 ± 1.0 mg/dL, P < 0.1), whereas a significant decrease in fasting serum insulin was observed (11.2 ± 6.1 versus 8.2 ± 2.9 mIU/mL, P < 0.05) and the reduction persisted after return to the regular diet. A slight but not significant reduction in urinary uric acid and fractional uric acid excretion was observed while the patients were on the low fructose diet. The low-fructose diet also decreased high sensitivity C-reactive protein (hsCRP) (4.3 ± 4.9 versus 3.3 ± 4.5 mg/L; P < 0.01) and soluble intercellular adhesion molecule (sICAM) (250.9 ± 59.4 versus 227 ± 50.5 ng/mL; P < 0.05). The hsCRP returned to baseline with resumption of the regular diet, whereas the reduction in sICAM persisted. CONCLUSION Low-fructose diet in subjects with CKD can reduce inflammation with some potential benefits on BP. This pilot study needs to be confirmed by a larger clinical trial to determine the long-term benefit of a low-fructose diet compared to other diets in subjects with CKD.

Bone marrow progenitors from animals with chronic renal failure lack capacity of in vitro proliferation.

BACKGROUND An interesting way to regenerate a kidney is an autologous bone marrow transplantation. The aim of this study was to examine whether chronic kidney disease influenced bone marrow progenitors. METHODS Wistar male rats included group I (n = 4, chronic kidney disease 1/2, CKD 1/2) that underwent right nephrectomy. In group II (n = 3, chronic kidney disease 5/6, CKD 5/6) underwent removal of the right kidney and approximately one-third of the cortex of the left kidney. Animals in the control group (n = 4) were intact. Bone marrow cells obtained from femurs were separated using a CD34 Micro-Beads magnetic isolation kit. Isolated cells were counted using a trypan blue exclusion test. Numbers of isolated cells were presented as mean values with standard deviation with P < .05 considered significant. CD34(-) cells were cultivated and observed to the passage 6. RESULTS The CKD rat model was used for in vitro experiments. There were no differences in cell numbers isolated from control rats versus both CKD rats. No differences were observed in CD34(-) cells after separation when compared to controls. Cell morphology was similar in primary CD34(-) cultures during the first days of primary culture. CD34(-) primary cultures established from chronic renal failure rats collapsed within 2 weeks. No differences were found in CD34(+) cell number after isolation when compared with controls. These cells did not form a monolayer. Cells in cultures established from control animals resembled normal fibroblast-like morphology of mesenchymal stem cells during 3 months. CONCLUSIONS Bone marrow cells from chronic renal failure rats showed no capacity for in vitro proliferation. We speculated that bone marrow cells obtained from renal chronic failure patients may not be useful for autologous cell transplantation.

Influence of Different Stages of Experimental Chronic Kidney Disease on Rats Locomotor and Postural Skeletal Muscles Microcirculation

Background. Chronic kidney disease (CKD) is associated with muscle excess fatigue and diminished maximal whole body oxygen consumption, which in part could be depended on poor muscle microcirculatory network. The aim of this study was to assume the influence of different stages of CKD on microcirculation vessels in functionally different skeletal muscles—locomotor, the gastrocnemius muscle, and postural, the longissimus thoracis muscle. Methods. Male Wistar rats underwent sham operation (CON), uninephrectomy (CKD 1/2) and subtotal nephrectomy (CKD 5/6). Muscle samples were stained for an alkaline phosphatase to differentiate capillaries. The number of capillaries was estimated by a single observer in 10 μm transverse sections by point counting at a magnification of ×125 using an Image Analysis System Q 500 MC of Leica. Blood pressure and serum creatinine, haptoglobin, MCP-1, VEGF, and PDGF were measured. Results. There were significant differences (p < 0.05) in CD (number of capillaries per 1 mm2 of muscle tissue), C:F (capillary to fiber ratio), and CC/F (capillary contact per fiber). The CKD 1/2 group in gastrocnemius and longissimus muscle had 53% and 33% lower C:F; 56% and 33% lower CD; and 44% and 20% less CC/F than CON, respectively. The CKD 5/6 group in gastrocnemius and longissimus muscle had 46% and 20% lower C:F; 47% and 11% lower CD; and 48% and 25% less CC/F versus control, respectively. Blood pressure was higher in CKD 5/6 vs. CKD 1/2 and CON (145/95 vs. 107/87 and 119/77 mmHg, p < 0.05, respectively). CKD 5/6 had higher creatinine than CKD 1/2 and CON (1.22 vs. 0.83 and 0.74 mg/dL, p < 0.05, respectively). Haptoglobin was higher in CKD 1/2 and CKD 5/6 versus CON (1.68 and 1.63 vs. 0.70 mg/mL, p < 0.05, respectively). MCP-1 was higher in CKD 5/6 and CKD 1/2 versus CON (609 and 489 vs. 292 pg/mL, p < 0.05, respectively). There were no significant differences in serum growth factors concentration between groups. Conclusion. Capillary rarefaction is present in early stages of CKD. These changes are independent of blood pressure and progression of CKD. We suspected that muscle function has a big impact on microvasculature as capillaries rarefaction has been reduced more in locomotor than postural skeletal muscle.

Decreased Hypoxia-Inducible Factor-1α in Gastrocnemius Muscle in Rats with Chronic Kidney Disease

Background/Aims: Hypoxia-inducible factor (HIF)-1α is responsible for increased expression of genes engaged in angiogenesis. Our previous study indicated capillary rarefaction and atrophy of glycolytic fibers, mainly in locomotor muscles of uremic animals. Perhaps these changes are secondary to disturbances of HIF-1α in skeletal muscles. Methods: Expression of HIF-1α at mRNA and protein levels, as well as mRNA of vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), in gastrocnemius muscle (MG) and longissimus thoracic muscle (ML) were measured by RT-PCR and Western blot. Rats were randomized to subtotal nephrectomy (CKD5/6), uninephrectomy (CKD1/2) or sham operation (controls). Results: For CKD5/6 versus controls, mRNA levels for HIF-1α, VEGF-A, VEGFR-1 and VEGFR-2 were significantly reduced only in MG, while eNOS was significantly decreased and iNOS was significantly increased only in ML. Western blot analysis indicated significantly increased HIF-1α protein levels in MG and ML from CKD1/2 animals versus controls, whereas in the CKD5/6 group, the level of HIF-1α protein decreased significantly in MG and increased significantly in ML versus controls and CKD1/2. Conclusion: The reduced expression of HIF-1α mRNA and protein in locomotor muscle from CKD5/6 animals may be involved in the pathogenesis of uremic myopathy. Increased expression of iNOS in the postural muscles may act as a protective factor through HIF-1α stabilization.

Impact of fructose diet and renal failure on the function of pancreatic islets.

Objectives This study was designed to evaluate the impact of fructose-rich diet and chronic kidney disease (CKD) on the in vitro function of pancreatic islets. Methods Fifty-four rats were divided into 3 equal groups as follows: control, rats with CKD 1/2 that underwent surgical uninephrectomy, and rats with CKD 5/6 that underwent uninephrectomy and kidney cortex mass resection. Each group was further assigned to 3 diet protocols—regular diet, regular diet with 10% fructose (F10), and 60% fructose-rich diet (F60). After 8 weeks of insulin administration, C-peptide, glycated hemoglobin level, serum urea nitrogen, creatinine clearance, and homeostasis model assessment of insulin resistance were evaluated. Static glucose insulin stimulation test of isolated pancreatic islets and histologic analysis of pancreatic tissue were performed. Results The F10 diet increased the levels of insulin and C-peptide in all groups. Homeostasis model assessment of insulin resistance was increased in all animals fed with fructose. The elevated levels of creatinine and diminished creatinine clearance were detected in CKD 5/6 rats fed with 60% fructose-rich diet. The F10 diet resulted in high levels of serum insulin and C-peptide and glucose-stimulated insulin secretion. Fructose-rich diet increased the islet size and number, with irregular morphology and exocrine tissue fibrosis. Conclusions The fructose-rich diet accelerates the progression of CKD and affects the pancreatic islet function.