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Online Library: Kidney Disease

The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting kidney disease. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

We encourage you to forward the link to this important online library on natural health – one of the largest ones in the world – to your friends. You may also print out the articles you find most important for your own health condition and share them with your doctor. Any responsibly acting health professional will be grateful to receive such science-based health education.

Low Lycopene Levels Found in Patients with Chronic Kidney Disease

Source: Nutrition, 2010; 26(3): 276-82

Author: Chiang SS, Tai CW, et al

Affiliation: Department of Internal Medicine/Nephrology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

Abstract: In a hospital-based, case-control study involving 201 patients with chronic kidney disease and 313 controls, low plasma lycopene levels were found to be associated with risk of chronic kidney disease. The authors conclude, "This is the first study showing that a low plasma lycopene level is associated with CKD risk."

Cholecalciferol Supplementation May Benefit Children With Chronic Kidney Disease

Source: Pediatr Nephrol, 2010;25(12):2483-2488

Author: Hari P, Bagga A, et al

Affiliation: India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Abstract: In a prospective intervention study involving 42 children (mean age = 7.7 years) with chronic kidney disease, results indicate a high prevalence of vitamin D insufficiency which may be corrected with high-dose cholecalciferol supplementation. The authors of this study conclude, "vitamin D insufficiency is highly prevalent in children with CKD stages 2-4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children."


Platelet Nitric Oxide Synthesis in Uremia and Malnutrition: a Role for L-Arginine Supplementation in Vascular Protection?

Source: Cardiovascular Research 2007; 73(2): 359-367.

Author: Brunini T.M., Mendes-Ribeiro A.C., Ellory J.C., Mann G.E.

Affiliation: Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-030, Brazil

Abstract: The aim of this review is to evaluate whether disturbances in the L-arginine-NO signalling pathway in chronic renal failure and atherosclerosis are affected by malnutrition and inflammation. L-arginine is the physiological precursor for nitric oxide (NO) synthesis, and availability and transport of L-arginine modulate the rates of NO biosynthesis in circulating blood cells and the vasculature. This study has established that reduced plasma L-arginine and NO production and increased tumour necrosis factor-alpha (TNF-alpha), fibrinogen, and C-reactive protein levels in malnourished uremic patients are associated with increased aggregability of platelets. The findings may explain the increased cardiovascular mortality in patients with deficient nutritional status, leading to inflammation, oxidative stress, impaired L-arginine-NO signalling, and platelet activation.

Nitric Oxide, Malnutrition and Chronic Renal Failure

Source: Cardiovascular and Hematological Agents in Medicinal Chemistry 2007; 5(2): 155-61

Author: Brunini T.M., Moss M.B., Siqueira M.A., Santos S.F., Lugon J.R., Mendes-Ribeiro A.C.

Affiliation: Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract: Chronic renal failure (CRF) is a complex clinical condition associated with accelerated atherosclerosis and thrombosis leading to cardiovascular events. There is considerable literature demonstrating that a disturbance in the nitric oxide control mechanism plays a role in mediating the haemodynamic and haemostatic disorders present in CRF. This article summarizes the current knowledge of L-arginine-nitric oxide pathway and malnutrition in chronic renal failure (CRF) and briefly describes possible therapeutic interventions. The conditionally essential amino acid L-arginine is the substrate for nitric oxide (NO) synthesis, a key second messenger involved in physiological functions including endothelium-dependent vascular relaxation and inhibition of platelet adhesion and aggregation. Extracellular L-arginine transport seems to be essential for the production of NO by the action of NO synthases (NOS), even when the intracellular levels of L-arginine are available in excess (L-arginine paradox).

Plasma Amino Acid Profile and L-Arginine Uptake in Red Blood Cells from Malnourished Uremic Patients

Source: Journal of Renal Nutrition 2006; 16(4): 325-31

Author: Reis P.F., da Silva C.D., Brunini T.M., Moss M.B., Siqueira M.A., Santos S.F., Roberts N.B., Ellory J.C., Mann G.E., Mendes-Ribeiro A.C.

Affiliation: Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract: Patients with end-stage chronic renal failure (CRF) (uremia) have a high prevalence of inflammation, malnutrition, and oxidative stress. The present study investigates the effects of nutritional status on L-arginine transport (NO precursor), plasma amino acid profile, and concentration of tumor necrosis factor (TNF)-alpha in uremic patients on hemodialysis (HD). L-arginine influx by system y(+) in red blood cells (micromol/L cells(-1)h(-1)) was increased in both malnourished (377 +/- 41) and well-nourished (461 +/- 63) patients with CRF compared with controls (287 +/- 28). Plasma levels of all cationic amino acids (L-arginine, L-ornithine, and L-lysine) were low in uremic patients compared with controls. Among the uremic population, the reduction in plasma cationic amino acids levels was greater in malnourished patients. The results suggest an increased catabolism of cationic amino acids, inflammatory markers, and oxidative stress in CRF, especially in malnourished patients. The reduced plasma concentration of plasma L-arginine is counterbalanced by enhanced rates of transport, resulting in an activation of NO synthesis in uremia.

Dr. Rath's Cellular Nutrient Synergy Program

A Nutrient Mixture Attenuates Acetaminophen Hepatic and Renal Toxicity in ICR Mice

Source: Published in: The Toxicologists (suppl. Toxicological Sciences) 2006; 90(1): Abstract 1398, p.285

Author: M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath

Affiliation: Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050

Abstract: “Overdosing with acetaminophen, a common over-the-counter analgesic, is often fatal, causing severe liver and kidney damage in humans and animals. A unique Dr. Rath’ nutrient formulation consisting of ascorbic acid, lysine, proline, and green tea extract (NM) has previously been demonstrated to exhibit a broad spectrum of pharmacological, therapeutic, cardio vascular and chemoprotective properties. This study was undertaken to determine whether NM is useful in treatment of APAP-induced hepatic and renal damage. Six-week-old male ICR mice were divided into four groups (A-D) of five animals each. APAP treatment (groups B and D) resulted in a marked increase in liver and kidney weights. Serum AST and ALT in groups A and C were comparable, increased markedly in group B and significantly reduced in group D. APAP caused significant centrilobular necrosis in group B animals, while NM prevented these alterations in group D. Serum markers of kidney: BUN, creatinine and BUN/creatinine ratio were markedly increased in group B in contrast to groups A and C. The NM fed group D exhibited biochemical parameters similar to control group A. The kidney of APAP intoxicated mice (B) showed severe acute damage to the glomerulus and proximal tubule in contrast to the kidneys of mice fed with NM (D), which demonstrated a nearly normal histological pattern. The results indicate that NM has potential to protect against APAP-induced liver and kidney damage.”


Synergistic Effect of Green Tea Polyphenols on their Protection Against FK506-Induced Cytotoxicity in Renal Cells

Source: The American Journal of Chinese Medicine 2008; 36(3): 615-24

Author: Hisamura F., Kojima-Yuasa A., Huang X., Kennedy D.O., Matsui-Yuasa I.

Affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Osaka 558-8585, Japan.

Abstract: The nephrotoxicity induced by FK506 remains a serious clinical problem. This study has examined the synergistic effect of tea polyphenols on the protection of FK506-induced cell death. The combined treatment with 5 microM (-)-epigallocatechin-gallate (EGCG) and 5 microM of (+)-catechin (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC) or epicatechin-gallate (ECG) reduced FK506-induced cytotoxicity in LLC-PK1. Similarly, the combined treatment with 5 microM EGC and 5 microM of C, EC, EGCG or ECG also reduced the cytotoxicity. These results showed that the co-treatments with EGCG and EGC, EGCG or ECG, and EGC and ECG have stronger synergistic effects on the protection of FK506-induced cell death. Furthermore, the combined treatment of EGCG (5 microM) and EGC (5 microM) showed a significant time-dependent suppression of the increased intracellular ROS levels 15 min after the addition of FK506, as well as on caspase activation. The results of these synergistic effects of the constituents of green tea extract suggest that its protective effects may reside in more than just one of its constituent.

Epigallocatechin 3-O-Gallate (EGCG)-Induced Apoptosis in Normal Rat Kidney Interstitial Fibroblast (NRK-49F) Cells

Source: Journal of Toxicological Sciences 2008; 33(3): 367-370

Author: Miyamoto Y., Sano M., Haylor J.L., El Nahas A.M.

Affiliation: Sheffield Kidney Institute, Northern General Hospital NHS Trust, The University of Sheffield, UK.

Abstract: Epigallocatechin 3-O-gallate (EGCG), a major catechin in green tea, suppresses renal failure in animals, and inhibits the growth of mesangial cells and opossum kidney proximal tubular cells. In addition, gallic acid, a structural constituent of this catechin, induces apoptosis in tumor cell lines. However, the effects of catechins on renal fibroblastic cells have not been investigated. In this experiment, the growth of normal rat kidney interstitial fibroblast (NRK-49F) cells was significantly inhibited by EGCG at concentrations higher than 6.25 microM, and almost completely inhibited at concentrations over 200 microM. The numbers of in situ end-labeled (ISEL) cells in cultures treated with EGCG at 6.25 to 200 microM increased dose-dependently. Furthermore, exposure to 6.25 to 50 microM EGCG for 24 hr led to a significant increase in caspase-3 activity compared to the control. These results suggest that EGCG induces apoptosis in NRK-49F cells.

Therapeutic Potential of (-)-Epigallocatechin 3-O-Gallate on Renal Damage in Diabetic Nephropathy Model Rats

Source: The Journal of Pharmacology and Experimental Therapeutics 2006; 19(1): 228-36.

Author: Yamabe N., Yokozawa T., Oya T., Kim M.

Affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Abstract: This study examined whether (-)-epigallocatechin 3-O-gallate (EGCg), the main polyphenolic compound, could ameliorate the development of diabetic nephropathy. Rats with subtotal nephrectomy plus STZ injection were orally administrated EGCg at doses of 25, 50, and 100 mg/kg body weight/day. After a 50-day administration period, EGCg-treated groups showed suppressed hyperglycemia, proteinuria, and lipid peroxidation, although there were only weak effects on the levels of serum creatinine and glycosylated protein. Furthermore, EGCg reduced renal advanced glycation end-product accumulation and its related protein expression in the kidney cortex as well as associated pathological conditions. These results suggest that EGCg ameliorates glucose toxicity and renal injury, thus alleviating renal damage caused by abnormal glucose metabolism-associated oxidative stress involved in renal lesions of diabetic nephropathy.

Effects of Green Tea on Urinary Stone Formation: an In Vivo and in Vitro Study

Source: Journal of Endourology 2006; 20(5): 356-61

Author: Jeong B.C., Kim B.S., Kim J.I., Kim H.H.

Affiliation: Department of Urology, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.

Abstract: This study evaluated whether epigallocatechin gallate (EGCG), a main constituent of green tea polyphenols, could protect against cellular toxicity by oxalate and whether green tea supplementation attenuates the development of nephrolithiasis in an animal model. Cells of the NRK-52E line were incubated with different concentrations of oxalate with and without EGCG, and toxicity and malondialdehyde assays were done to investigate the cytotoxic effect of oxalate and the anti-oxalate effect of EGCG. The results show that as oxalate concentrations increased, the number of surviving cells decreased, and the formation of free radicals increased. The administration of EGCG inhibited free-radical production induced by oxalate. Green tea supplementation decreased the excretion of urinary oxalate and the activities of urinary gammaglutamyltranspeptidase and N-acetylglucosaminidase. The number of crystals within kidneys in group 3 was significantly lower than in group 2. The study concludes that green tea has an inhibitory effect on urinary stone formation, and the antioxidative action of EGCG is considered to be involved.

Effect of Epigallocatechin Gallate on Renal Function in Cyclosporine-Induced Nephrotoxicity

Source: Transplantation Proceedings 2004; 36(7): 2133-2134.

Author: Chang E.J., Mun K.C.

Affiliation: Dong San Kidney Institute and Chronic Disease Research Center, Keimyung University School of Medicine, Daegu, Korea.

Abstract: The purpose of the present study was to investigate the protective effect of EGCG in a rodent model. Experiments were performed on 3 groups. The normal control group (group 1) received normal saline solution. The CsA-treated group (group 2; 15 mg/kg body weight/d for 14 days) received subcutaneous injections. The EGCG-treated group (group 3) in addition received 25 mg of EGCG/kg body weight by intraperitoneal injection. The results show that EGCG treatment significantly protected renal function and free radical-mediated injury in the kidney from CsA-induced changes.


Drug Discovery for Overcoming Chronic Kidney Disease (CKD): Prolyl-Hydroxylase Inhibitors to Activate Hypoxia-Inducible Factor (HIF) as a Novel Therapeutic Approach in CKD

Source: Journal of Pharmacological Sciences 2009; 109(1): 24-31

Author: Tanaka T., Nangaku M.

Affiliation: Division of Nephrology and Endocrinology, University of Tokyo Hospital and School of Medicine, Tokyo, Japan.

Abstract: Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor composed of an oxygen-dependent alpha-subunit and constitutively expressed beta subunit, which plays a central role in cellular adaptation to hypoxia by transcriptionally upregulating its target genes involved in angiogenesis, erythropoiesis, glycolysis, and so on. Recent studies demonstrated that hypoxia in the tubulointerstitium is involved in the pathology of progressive renal diseases and that HIF, which is activated in experimental kidney diseases, may serve to protect tubulointerstitium from the ischemic insult. The expression of HIF alpha-chains is post-translationally regulated and hydroxylation at one or two of the conserved proline residues by prolyl-hydroxylase domains (PHDs) is a critical step for the oxygen-dependent recruitment of the von Hippel-Lindau gene product (pVHL), a recognition component of the E3 ubiquitin ligase complex, and degradation of HIF-alpha. Conversely, modalities to inhibit the enzymatic activities of PHDs have been shown to activate HIF irrespective of oxygenation status and are regarded as candidate targets of pharmacological approaches against chronic kidney diseases characterized by hypoxia.

N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Prevents Renal Insufficiency and Mesangial Matrix Expansion in Diabetic db/db Mice

Source: Diabetes 2005; 54(3): 838-845.

Author: Shibuya Kazuyuki;1 Kanasaki Keizo;1 Isosno Motohide;1 Sato Haruhisa;2 Omata Mitsugu;3 Sugimoto Toshiro;1 Araki Shin-Ichi;1 Isshiki Keiji;1 Kashiwagi Atsunori;1 Haneda Masakazu;4 Koya Daisuke1

Affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan;1 Marutamachi Otowa Hospital, Kyoto, Japan;2 Daiichi Suntory Biomedical Research, Mishima, Osaka, Japan;3 Second Department of Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan4

Abstract: It was previously reported that N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is a tetrapeptide hydrolyzed by ACE, inhibits the transforming growth factor-β (TGF-β)-induced expression of extracellular matrix proteins via inhibition of the Smad signaling in human mesangial cells. This study examined whether long-term Ac-SDKP treatment can prevent renal insufficiency and glomerulosclerosis in diabetic db/db mice. This study shows that treatment with Ac-SDKP increased plasma Ac-SDKP concentrations by approximately threefold in both groups but did not affect the blood glucose levels. These results demonstrate that long-term Ac-SDKP treatment ameliorates renal insufficiency and glomerulosclerosis in db/db mice via inhibition of TGF-β/Smad pathway, suggesting that Ac-SDKP could be useful in the treatment of diabetic nephropathy.

Vitamin C

The Protective Effects of Ascorbic Acid Against Renal Ischemia-Reperfusion Injury in male Rats

Source: Renal Failure 2009; 31(1): 36-43

Author: Korkmaz A., Kolankaya D.

Affiliation: Department of Biology, Hacettepe University, Ankara, Turkey.

Abstract: This study was designed to investigate the effects of ascorbic acid (AA) in I/R-induced renal injury in rats. Thirty two male Sprague-Dawley rats were divided equally into four groups. Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. I/R caused a significant decrease in GSH level, which was accompanied with a significant increase in MDA level of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH, were elevated in the I/R group as compared to the control group. In group four, AA treatment reversed all the changes in these biochemical indices, as well as histopathological alterations normally induced by I/R. The findings imply that reactive oxygen species play a causal role in I/R-induced renal injury, and that AA exerts renoprotective effects, probably by radical scavenging and antioxidant activities.

Vitamin C with Metabolites Reduce Oxalate Levels Compared to Ascorbic Acid: a Preliminary and Novel Clinical Urologic Finding

Source: Urological Nursing 2009; 29(2): 95-102

Author: Moyad M.A., Combs M.A., Crowley D.C., Baisley J.E., Sharma P., Vrablic A.S., Evans M.

Affiliation: University of Michigan Medical Center, Department of Urology, Ann Arbor, MI, USA.

Abstract: The incidence and prevalence of kidney stones are notable and are projected to increase over the next decade. Risk factors for kidney stones abound, but a prominent risk factor is hyperoxaluria, which has numerous etiologies, including vitamin C (ascorbic acid) dietary supplement intake. This randomized, double-blind, crossover study examined the effects of two different vitamin C formulations and found that vitamin C with metabolites (Ester-C) significantly reduced urine oxalate levels compared to ascorbic acid. This is a potential novel finding that requires further clinical evaluation.

The Role of vitamin C, Vitamin E, and Selenium on Cadmium-Induced Renal Toxicity of Rats

Source: Drug and Chemical Toxicology 2008; 31(4): 413-26

Author: Karabulut-Bulan O., Bolkent S., Yanardag R., Bilgin-Sokmen B.

Affiliation: Department of Biology, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey.

Abstract: The aim of this study was to determine whether vitamin C, vitamin E, and selenium have protective effects against cadmium-induced renal toxicity of rats. Vitamin C (250 mg/kg/day), vitamin E (250 mg/kg/day), and sodium selenate (0.25 mg/kg/day) were given to rats orally for 8 days. Cadmium (2 mg/kg/day CdCl2) was given to rats intraperitoneally. Vitamin C, vitamin E, and selenium (in the same dose and time) were given 1 h prior to the administration of cadmium every day. The damage to the kidney tissue was moderate in the rats given cadmium. In this group, the distinctive changes in the proximal tubules were observed. Degenerative changes in kidney tissue were also observed in rats given vitamin C, vitamin E, selenium, and cadmium. Serum urea and creatinine levels were also increased in rats given cadmium. The administration of vitamin C, vitamin E, and selenium caused a significant decrease in LPO levels and an increase in GSH levels in the kidney of rats given cadmium. Serum urea and creatinine levels were decreased in rats given both the antioxidant and cadmium. It is concluded that vitamin C, vitamin E, and selenium showed some protective effect on the rat kidney.

Oral Vitamin C Supplementation in Hemodialysis Patients and Its Effect on the Plasma Level of Oxidized Ascorbic Acid and Cu/Zn Superoxide Dismutase, an Oxidative Stress Marker

Source: Nephron Clinical Practice 2008; 109(2): c49-54.

Author: Washio K., Inagaki M., Tsuji M., Morio Y., Akiyama S., Gotoh H., Gotoh T., Gotoh Y., Oguchi K.

Affiliation: Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.

Abstract: Oxidative stress is known to be enhanced in hemodialysis patients, and one of its useful markers is plasma copper/zinc superoxide dismutase (Cu/Zn-SOD). This study examined the antioxidative effects of water-soluble vitamin C administered orally on Cu/Zn-SOD levels in hemodialysis patients. Vitamin C was orally administered to 16 maintenance hemodialysis patients before each dialysis session. Doses were increased from 200 to 1,000 mg over 3 months. The levels of plasma vitamin C and Cu/Zn-SOD and its mRNA expression in leukocytes were determined 1, 2, and 3 months after the start of vitamin C administration. Following oral administration, the plasma levels of vitamin C and its oxidized form were increased. However, significant changes in plasma Cu/Zn-SOD or its mRNA expression in leukocytes were not observed. The study concludes that in maintenance hemodialysis patients, vitamin C administration resulted in a significant increase in the postdialysis level of the oxidized form of vitamin C, which suggested an increase in antioxidant effect. However, water-soluble vitamin C did not significantly suppress Cu/Zn-SOD expression enhancement.

Scurvy Diagnosed in a Pediatric Liver Transplant Patient Awaiting Combined Kidney and Liver Retransplant

Source: Pediatric Transplantation 2008; 12(3): 363-7.

Author: Samonte V.A., Sherman P.M., Taylor G.P., Carricato M.N., Fecteau A., Ling S.C., Ng V.L.

Affiliation: Pediatric Academic Multi Organ Transplant (PAMOT) Program, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Abstract: A 15-yr-old girl underwent liver transplantation at age 26 months for a primary diagnosis of biliary hypoplasia, and subsequently developed late allograft failure and progressive renal insufficiency culminating in listing for combined liver retransplantation and kidney transplantation at age 13 yr. She required regular hemodialysis treatment for 12 months prior to deceased donor organ availability, with a complicated clinical course including recurrent septic episodes and severe cachexia. Ten months after initiation of hemodialysis, she presented with severe bone pain, purpura, ecchymoses, gingival hyperplasia, mucosal bleeding, and subconjunctival hemorrhages. Serial serum ascorbic acid levels were found to be extremely low (<10 micromol/L) despite routine supplementation both in her dialysate and via regular oral supplementation. Histopathology from skin biopsy revealed purpura, hyper- and parakeratosis, and follicular plugging. She had ECG and 2D echocardiogram disturbances, as well as osteopenia and sclerosis of the extremities on radiological evaluations. Therapy with high-dose ascorbic acid (1 g/day orally) led to complete resolution of skin lesions. This case highlights the importance of awareness and recognition of this historic diagnosis, and particularly in children with end-stage organ disease with severely compromised nutrition.

Vitamin C Deficiency and Secondary Hyperparathyroidism in Chronic Haemodialysis Patients

Source: Nephrol Dial Transplant 2008; 23(6): 2058-63.

Author: Richter A., Kuhlmann M.K, Seibert E., Kotanko P., Levin N.W., Handelman G.J.

Affiliation: Renal Research Institute, 207 East 94th Street, Suite 303, New York, NY 10128, USA.

Abstract: This study examined serum bio-intact parathyroid hormone (BiPTH) and plasma vitamin C in 117 chronic haemodialysis patients. Plasma vitamin C showed a significant positively skewed distribution, ranging from <2 microM to >300 microM. The results indicate that 15% (n = 17) of the patients have severe vitamin C deficiency (<10 microM), 66% (n = 77) in the range 10-80 microM, and 19% (n = 23) with plasma vitamin C >80 microM, the upper limit of normal for non-renal disease population. High plasma vitamin C was associated with lower plasma BiPTH (P = 0.005, one-way analysis of variance), and this association persisted after stepwise multiple regression for other factors known to influence PTH. Low vitamin C levels were also associated with increased serum alkaline phosphatase, a further indicator of the impact of vitamin C status on bone metabolism. Patients who reported dietary vitamin C intake of >or=100 mg/day had lower BiPTH (P = 0.015), consistent with findings from plasma measurements of vitamin C. This novel observation of the interaction between PTH and vitamin C may result. This finding does not yet warrant therapeutic intervention with supplemental vitamin C to remedy secondary hyperparathyroidism. However, further research may indicate a key interaction between vitamin C and the parathyroid hormone linked signalling pathways, and may uncover mechanisms of therapeutic importance.

Effects of Melatonin and Vitamin C on Cigarette Smoke-Induced Damage in the Kidney

Source: Toxicology and Industrial Health 2007; 23(8): 479-85

Author: Ozan E., Sonmez M.F., Ozan S., Colakoglu N., Yilmaz S., Kuloglu T.

Affiliation: Medical Faculty, Histology and Embryology Department, Firat University, Elazig, Turkey.

Abstract: This study was carried out to investigate smoke-induced structural and biochemical changes and protective effects of co-administered melatonin and vitamin C in the kidney. Twenty-four Wistar adult female rats were used in this study and they were divided into four groups. Malondialdehyde and glutathione levels and catalase activity were determined. By light microscopic observation, a decrease of Bowman space of some renal corpuscles, foamy-like tubules, dilatation and congestion of the peritubuler vessels, and atrophy of the some renal corpuscles were observed in group II. In groups III and IV melatonin and vitamin C relatively protected the kidney tissue against smoke intoxication. Melatonin and vitamin C injection to group III and IV caused a decrease in malondialdehyde and glutathione levels. This study has shown that cigarette smoke inhalation caused structural changes in the kidney. However, melatonin and vitamin C administration produced in some degree protection against smoke-induced damage.

High Prevalence of Ascorbate Deficiency in an Australian Peritoneal Dialysis Population

Source: Nephrology (Carlton) 2008; 13(1): 17-22

Author: Singer R., Rhodes H.C., Chin G., Kulkarni H., Ferrari P.

Affiliation: School of Medicine and Pharmacology, University of Western Australia and Department of Nephrology, Fremantle Hospital, Perth, Western Australia, Australia.

Abstract: Requirements for ascorbate are increased in peritoneal dialysis (PD) patients most likely due to a combination of poor nutrition and increased dialysate losses. This study measured serum ascorbate levels in 45 clinically stable PD patients to assess the prevalence of ascorbate insufficiency (level between 2 and 4 mg/L) and deficiency (level <2 mg/L). It also assessed the efficacy of subsequent supplementation and patients' adherence to the prescribed supplementation. All patients were advised on commencement of dialysis to take a multivitamin tablet containing 100-120 mg ascorbate. The results show that, in PD patients, ascorbate deficiency is common and can readily be identified with serum ascorbate measurements. Oral supplements in the form of inexpensive multivitamin preparations restore adequate serum ascorbate levels in the majority of these patients. The study therefore suggests measurement of ascorbate levels in all PD patients at the commencement of dialysis with a target level in the normal range (4-14 mg/L).

Protective Effects of Vitamin C on Cisplatin-Induced Renal Damage: a Light and Electron Microscopic Study

Source: Renal Failure 2008; 30(1): 1-8

Author: Tarladacalisir Y.T., Kanter M., Uygun M.

Affiliation: Department of Histology and Embryology, Faculty of Medicine, Trakya University, Edirne, Turkey.

Abstract: The present study was performed to investigate whether the chronic administration of antioxidant vitamin C provided morphological protection on cisplatin-induced renal damage. Wistar albino male rats were divided into control and two experiment groups, each consisting of six rats. Cisplatin (5 mg/kg/month) was administered intravenously to the second and third group for three months. After the first application of cisplatin, vitamin C (8 mg/kg/day) to the third group was administered intramuscular for 3 months. At the end of the third month, the kidney specimens of the all groups were obtained. The most obvious changes were encountered in the proximal tubules. These changes were tubular dilation, thickening of basement membrane, loss of brush border, vacuolization, and swollenness of mitochondria in the proximal tubule epithelial cells. In addition, infiltration foci were observed mainly in the cortical region. In the third group, which was administered cisplatin plus vitamin C, although the structural damages and morphometric changes were lessened, mononuclear cell infiltration was still observed. This study suggests that the chronic administration of vitamin C may be of therapeutic benefit on cisplatin nephrotoxicity.

Lipid Peroxidation in Hemodialysis Patients: Effect of Vitamin C Supplementation

Source: Clinical Biochemistry 2008; 41(6): 381-6.

Author: Ferretti G., Bacchetti T., Masciangelo S., Pallotta G.

Affiliation: Istituto di Biochimica, Università Politecnica delle Marche Via Ranieri, 60131, Ancona, Italy.

Abstract: Aim of the study was to further investigate the relationship between oxidative stress and chronic renal failure. The study compared the paraoxonase (PON1) activity, the levels of lipid hydroperoxides and AGE adducts in plasma of hemodialysis patients before and after intravenous administration of vitamin C. An increase in lipid hydroperoxides, AGE adducts and a decrease in the activity of PON1 were observed in patients with respect to controls. The comparison before and after supplementation with vitamin C showed an increase of PON1 activity and a decrease of AGE and lipid hydroperoxides levels. The results provide further evidence that lipid peroxidation and impairment of antioxidant system in plasma of patients may play a role in renal disease and suggest that evaluation of PON1 activity could represents an useful approach to monitor antioxidant treatment and new dialysis therapies.

The Effects of Iloprost and Vitamin C on Kidney as a Remote Organ after Ischemia/Reperfusion of Lower Extremities

Source: The Journal of Surgical Research 2007; 140(1): 20-6.

Author: Ozcan A.V., Sacar M., Aybek H., Bir F., Demir S., Onem G., Goksin I., Baltalarli A., Colakoglu N.

Affiliation: Department of Cardiovascular Surgery, Denizli, Turkey.

Abstract: This study investigated the effects of iloprost and vitamin C on the kidney remote organ damage after I/R following abdominal aortic surgery. Thirty-four adult male Wistar rats were used and divided into five groups. I/R was studied infrarenally in the abdominal aorta following a median laparotomy. Group III (n = 6, control group) was subjected to 3 h of ischemia followed by an hour of reperfusion. Group IV (n = 8) was given iloprost 20 ng/kg/min during I/R period before aortic-clamping. Group V (n = 8) was given vitamin C 100 mg/kg during I/R period before aortic-clamping. While the arterial blood pO(2) and HCO(3) levels significantly increased, the plasma and renal parenchymal MDA levels significantly decreased in both group IV and group V when compared to group III (P < 0.05). Histopathological and acute inflammation scores statistically decreased in both group IV and V compared with group III (P < 0.05). Although MDA levels, histopathologic and acute inflammation scores in group V were lower than group IV, the differences were not statistically significant (P > 0.05). the study concludes that both iloprost and vitamin C decreased remote organ damage on the kidney after I/R of lower extremities in the rat model. However, vitamin C is more effective than iloprost in preventing postoperative renal dysfunction.

Vitamin D

Vitamin D status in children with renal diseases. (translation from Polish)


Author: Pańczyk-Tomaszewska M, et al.

Affiliation: Katedra i Klinika Pediatrii i Nefrologii WUM, Warszawa, Poland.

Abstract: The aim of this study is the assessment of vitamin D status in children with selected renal diseases based on serum 25OHD3 level taking into consideration type of kidney disease, vitamin D supplementation and season of the year. Retrospective analysis of 127 children aged from 0.6 to 17.7 years, median 9.5 [24 with risk status of urolithiasis (RSU), 29 with urolithiasis, 15 with glomerulonephritis, 59 with idiopathic nephrotic syndrome (INS)] was performed. Serum concentrations of 25OHD3, 1,25(OH)2 D3, calcium, and phosphorus were measured. The correlation of 25OHD3 with the type of kidney disease, supplementation of vitamin D, seasons, gender, age, and the dose of glucocorticosteroids (in children with glomerulopathies) were analyzed. In all children serum concentration of 25OHD3 from 4.3 to 72.6 ng/mL (median 21.1 ng/mL). The deficiency or insufficiency of vitamin D were observed in 55 (43.3%) analyzed children with kidney diseases. The deficiency or insufficiency of vitamin D were observed in 49.1% children with RSU and urolithiasis, and in 39.2% with glomerulonephritis and INS: in 36% children supplemented with vitamin D and 54% not supplemented (NS). In winter, 25OHD3 serum concentration was significantly higher in children supplemented with vitamin D compared to not supplemented [median 21.5 ng/mL vs 16.5 ng/mL]. There were no significant differences in serum concentrations of 25OHD3 , 1,25(OH)2 D3 , calcium, phosphorus and calcium x phophorus product depending on type of kidney disease and gender. The significant negative correlation was found between 25OHD3 and patients' age and between calcium and calcium x phosphorus in children supplemented with vitamin D. The results suggest the necessity to develop new strategies in vitamin D supplementation in children with kidney diseases.


Dietary zinc is a key environmental modifier in the progression of IgA nephropathy.


Author: Maiguma M, Suzuki Y, Suzuki H, Okazaki K, Aizawa M, Muto M, Tomino Y.

Affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.

Abstract: IgA nephropathy (IgAN) shows diverse epidemiological characteristics, resulting from both genetic and acquired (e.g., environmental) causes. Environmental factors, such as diet or exposure to exogenous antigens, may prescribe the progression or prognosis of IgAN. It remains unclear as to how diet and infection influence susceptibility to IgAN. A relationship, such as Toll-like receptors (TLRs), especially TLR9 and TLR4, was demonstrated between IgAN and pathogen-recognition molecules. Recently, zinc (Zn) was discovered to be involved in various immune-related diseases, affecting B, T, and dendritic cells (DCs). This study investigates the relationship between dietary Zn and IgAN development in IgAN-prone mice. Seven-week-old IgAN-prone mice were divided into low, normal, and high Zn diet groups. To assess exogenous pathogen-mediated immune responses, lipopolysaccharide (LPS) was nasally administered. The activity of IgAN was biochemically and pathologically evaluated during the disease course. We also examined in vitro IgA production in spleen cells or in combinations of cocultured B, T, and DCs under various Zn conditions with or without LPS. Dietary conditioning with Zn affected serum immunoglobulins and urinary albumin levels, and mesangial deposition of IgA and IgG. Zn deficiency is associated with IgAN progression through the activation of the TLR4/TIR-domain-containing adapter-inducing interferon-â (TRIF), but not the TLR9, in DCs. Zn supplementation prevented disease aggravation. The findings of this study indicate that immune conditioning with dietary Zn alters nephritogenic IgA production after mucosal infection.