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Induction of renal damage in rats by a diet
deficient in antioxidants
Sadava D.; Luo P.-W.; Casper J.
Keck Science Center, 925 N. Mills Ave.,Claremont, CA 91711
United States
Nutrition Research (USA), 1996, 16/9 (1607-1612)
Male albino rats, age 28 days, were fed a diet containing
both vitamin E (10 g/kg) and selenium (5 mg/kg) or a diet
lacking these antioxidants. Animals were examined for renal
function after 4, 8, 12 and 16 wk on the respective diets.
After 8 wk, animals on the deficient diet weighed less than
controls (15%, p<0.01), and this became more pronounced by
16 weeks (25%, p<0.01). Expressed on a body weight basis,
kidney wet weights did not differ between the two groups of
animals. Urine volume increased in the animals fed the
deficient diet at 8 weeks (66%, p<0.01) and this was
maintained at 16 weeks (35%, p<0.01). Similar increases
were observed for the rates of excretion of urinary total
protein (77% elevation at 16 wk, p<0.01) and urinary acid
phosphatase (51% elevation, p<0.01). At 16 wk, the specific
activity of renal acid phosphatase in the animals given the
deficient diet was reduced in cortex (57%, p<0.01) and
medulla (20%, p<0.01), but not in papilla. These data
indicate that dietary antioxidant deficiency causes
progressive and pronounced renal damage.
Hyperhomocysteinemia confers an independent
increased risk of atherosclerosis in end-stage renal disease
and is closely linked to plasma folate and pyridoxine
concentrations.
Robinson K, Gupta A, Dennis V, Arheart K, Chaudhary D, Green
R, Vigo P, Mayer EL, Selhub J, Kutner M, Jacobsen DW
Department of Cardiology, Cleveland Clinic Foundation, OH
44195, USA
robinsk@ccsmtp.ccf.org
Circulation 1996 Dec 1;94(11):2743-8
BACKGROUND: A high level of total plasma homocysteine is a
risk factor for atherosclerosis, which is an important cause
of death in renal failure We evaluated the role of this as a
risk factor for vascular complications of end-stage renal
disease.
METHODS AND RESULTS: Total fasting plasma homocysteine and
other risk factors were documented in 176 dialysis patients
(97 men, 79 women; mean age, 56.3 +/- 14.8 years). Folate,
vitamin B12, and pyridoxal phosphate concentrations were also
determined. The prevalence of high total homocysteine values
was determined by comparison with a normal reference
population, and the risk of associated vascular complications
was estimated by multiple logistic regression. Total
homocysteine concentration was higher in patients than in the
normal population (26.6 +/- 1.5 versus 10.1 +/- 1.7 mumol/L; P
< .01). Abnormally high concentrations (> 95th
percentile for control subjects, 16.3 mumol/L) were seen in
149 patients (85%) with end-stage renal disease (P < .001).
Patients with a homocysteine concentration in the upper two
quintiles (> 27.8 mumol/L) had an independent odds ratio of
2.9 (CI, 1.4 to 5.8; P = .007) of vascular complications. B
vitamin levels were lower in patients with vascular
complications than in those without. Vitamin B6 deficiency was
more frequent in patients than in the normal reference
population (18% versus 2%; P < .01).
CONCLUSIONS: A high total plasma homocysteine concentration
is an independent risk factor for atherosclerotic
complications of end-stage renal disease. Such patients may
benefit from higher doses of B vitamins than those currently
recommended.
High dose-B-vitamin treatment of
hyperhomocysteinemia in dialysis patients.
Bostom AG, Shemin D, Lapane KL, Hume AL, Yoburn D, Nadeau MR,
Bendich A, Selhub J, Rosenberg IH
USDA Human Nutrition Research Center on Aging, Tufts New
England Medical Center, Boston, Massachusetts, USA.
Kidney Int 1996 Jan;49(1):147-52
Hyperhomocysteinemia, an arteriosclerotic risk factor,
persists in 75% of dialysis patients despite routine low dose
supplementation with the B-Vitamin-Co-factors/substrates for
homocysteine (Hcy) metabolism, and normal or supernormal
plasma status of these vitamins (Atherosclerosis 114:93,
1995). We conducted a placebo-controlled eight-week trial of
the effect on plasma homocysteine of adding supraphysiologic
dose folic acid (15 mg/day), B-6 (100 mg/day), and B-12 (1
mg/day) to the usual daily dosing of 1 mg folic acid, 10 mg
B-6, and 12 micrograms B-12, in 27 hyperhomocysteinemic
dialysis patients. Total plasma homocysteine was measured at
baseline, and after four and eight weeks. Blinded analyses
revealed no evidence of toxicity in the group randomized to
supraphysiologic dose B-vitamin supplementation. Plasma
homocysteine was significantly reduced after both four weeks
(-29.8% vs. -2.0%; P = 0.0024) and eight weeks (-25.8% vs.
+0.6%; P = 0.0009) of active versus placebo treatment. Also, 5
of 15 treated versus 0 of 12 placebo group patients had their
plasma Hcy reduced to within the normative range (< 15
mumol/liter). Supraphysiologic doses of B-vitamins may be
required to correct hyperhomocysteinemia in dialysis
patients.
Long-term folic acid (but not pyridoxine)
supplementation lowers elevated plasma homocysteine level in
chronic renal failure.
Chauveau P, Chadefaux B, Coude M, Aupetit J, Kamoun P,
Jungers P
Department of Nephrology, Necker Hospital, Paris,
France.
Miner Electrolyte Metab 1996;22(1-3):106-9
Moderate hyperhomocysteinemia, a risk factor for premature
atherosclerosis, is present in chronic uremic patients. We
prospectively evaluated the effects of sequential
supplementation with pyridoxine (70 mg/day) and folic acid (10
mg/day) for two 3-month periods in 37 nondialyzed patients (29
males) with creatinine clearance (Ccr) ranging from 10 to 80
ml/min, whose plasma vitamin B12 and folate level was in the
normal range. Mean (+/- SD) baseline plasma total homocysteine
(Hcy) was 14.9 +/- 5.2, 16.5 +/- 5.1 and 26.1 +/- 12.1 mumol/l
(upper limit in 45 healthy controls 14.1 mumol/l) in patients
with CCr 40-80, 20-40 and < 20 ml/min, respectively.
Following pyridoxine Hcy did not significantly decrease
whereas following folic acid Hcy decreased significantly to
9.9 +/- 2.9 (-33% vs. baseline), 10.3 +/- 3.4 (-37%) and 15.4
+/- 5.5 (-40%), respectively (Student's paired t test, p <
0.001) in the 3 groups. We conclude that folate (but not
pyridoxine) pharmacologic supplementation is effective in
lowering elevated plasma Hcy in chronic renal failure
patients, thus suggesting that enhancing the Hcy remethylation
pathway may overcome hyperhomocysteinemia in such patients. In
view of the potential atherogenic effects of
hyperhomocysteinemia, long-term folate supplementation should
be considered in uremic patients.
Taurine: A therapeutic agent in experimental kidney
disease
Trachtman H.; Sturman J.A.
Schneider Children's Hospital, Division Nephrology, SCH 365,
269-01 76th Avenue, New Hyde Park, NY 11040 USA
Amino Acids (Austria), 1996, 11/1 (1-13)
Taurine is an abundant free amino acid in the plasma and
cytosol. The kidney plays a pivotal role in maintaining
taurine balance. Immunohistochemical studies reveal a unique
localization pattern of the amino acid along the nephron.
Taurine acts as an antioxidant in a variety of in vitro and in
vivo systems. It prevents lipid peroxidation of glomerular
mesangial cells and renal tubular epithelial cells exposed to
high glucose or hypoxic culture conditions. Dietary taurine
supplementation ameliorates experimental renal disease
including models of refractory nephrotic syndrome and diabetic
nephropathy. The beneficial effects of taurine are mediated by
its antioxidant action. It does not attenuate ischemic or
nephrotoxic acute renal failure or chronic renal failure due
to sub-total ablation of kidney mass. Additional work is
required to fully explain the scope and mechanism of action of
taurine as a renoprotective agent in experimental kidney
disease. Clinical trials are warranted to determine the
usefulness of this amino acid as an adjunctive treatment of
progressive glomerular disease and diabetic nephropathy.
Kidney stone clinic: Ten years of experience
Jabor A.
Hospital Kladno, Vanurova 1548, CZ-27259 Kladno Czech
Republic
Nederlands Tijschrift voor de Klinische Chemie (Netherlands),
1996, 21/1 (8-10)
Experiences are described at a kidney stone clinic which
was established as part of the Department of Clinical
Biochemistry ten years ago. During this period, the
investigational protocol has changed from an in-patient to an
out-patient scheme. The most important metabolic abnormalities
among calcium oxalate kidney stone formers were
hypercalciuria, hypernatriuria, hyperuricosuria, increased
blood urate, decreased blood phosphate and hyperphosphaturia
with decreased renal phosphate threshold. These abnormalities
were found in the majority of patients. Oxalate output was,
however, increased in less than 50 percent of the patients.
The effectivity of thiazides, allopurinol, magnesium and
phosphate supplementation was tested, and it was concluded
that
(a) the effect of thiazides was significant, but calciuria
normalized only in a few cases,
(b) the withdrawal of allopurinol led to a significant
increase of urate parameters only in patients without a
low-purine diet,
(c) a sufficient dose of magnesium and phosphate is necessary
to achieve a therapeutie effect. Preliminary data indicate
that some patients with hypercalciuria and kidney stones are
at risk of decreased bone mass, and the role of bone markers
monitoring is mentioned.
Magnesium in the physiopathology and treatment of
renal calcium stones
Labeeuw M.; Pozet N.; Zech P.; Traeger J.
Clinique de Nephrologie, Pavillon P., Hopital Edouard
Herriot, 69374 Lyon Cedex France
Presse Med. (France), 1987, 16/1 (25-27)
The inhibitory effect of magnesium on the first stages of
renal calcium stone formation is modest in vitro and more
pronounced in experimental in vivo studies. Magnesium
deficiency has not yet been convincingly demonstrated in man.
However, urinary magnesium concentrations are abnormally low
in relation to urinary calcium concentrations in more than 25%
of patients with kidney stones. A supplementary magnesium
intake corrects this abnormality and prevents the recurrence
of stones. Magnesium seems to be as effective against stone
formation as diuretics. The modalities of magnesium therapy
still have to be determined and its results confirmed.
Magnesium, possibly added to drinking water, may well play a
role in the primary prevention of renal calcium stones.
Urinary factors of kidney stone formation in
patients with Crohn's disease
Bohles H.; Beifuss O.J.; Pichl J.; Akcetin Z.; Demling L.;
Brandl U.
Universitatskinderklinik, D-8520 Erlangen Germany, Federal
Republic of
Klin. Wochenschr. (Germany, Federal Republic of), 1988, 66/3
(87-91)
An increased frequency of kidney stone formation is
reported in patients with imflammatory bowel disease. In order
to investigate its pathogenesis, the concentrations of factors
known to enhance calcium oxalate stone formation (oxalate,
calcium, uric acid) as well as of inhibitory factors for
nephrolithiasis (magnesium, citrate) were determined in the
urine of 86 patients with Crohn's disease and compared with
those of 53 metabolically healthy controls. Six patients with
Crohn's disease already had experienced calcium oxalate
nephrolithiasis. Patients with Crohn's disease had
significantly higher urinary oxalate and lower magnesium and
citrate concentrations. Among all patients magnesium and
citrate were significantly lower in those with a positive
history of kidney stones. Our results demonstrate that the
increased propensity for renal stone formation in patients
with Crohn's disease is a result not only of increased urinary
oxalate, but also of decreased urinary magnesium and citrate
concentrations.
Renal stone formation in patients with inflammatory
bowel disease
Caudarella R.; Rizzoli E.; Pironi L.; Malavolta N.; Martelli
G.; Poggioli G.; Gozzetti G.; Miglioli M.; Rothstein R.D.;
Malet P.F.; Thomas W.C.; Bohles H.
Istituto di Patologia Medica II, Via Massarenti 9, 40138
Bologna Italy
Scanning Microsc. (USA), 1993, 7/1 (371-380)
Kidney stones are more common in patients with inflammatory
bowel disease (IBD) than in the general population. The main
lithogenetic risk factors were evaluated in patients affected
by Crohn's disease and ulcerative colitis. Our results show
the presence of several factors, besides hyperoxaluria, in
patients with IBD although their behaviour appears different
in Crohn's disease and ulcerative colitis at pre- and
post-operative stages. Before surgery in patients with Crohn's
disease we found a decreased citrate (p < 0.001) and
magnesium (p < 0.005) excretion together with a low urinary
volume (p < 0.001) and pH (p < 0.005). After surgery
patients with Crohn's disease showed a further reduction of
magnesium and citrate. Patients with ulcerative colitis before
surgery showed a reduced citrate excretion (p < 0.05) and a
more acidic pH (p < 0.05) than healthy subjects. Surgical
treatment of proctocolectomy with ileal pouch-anal anastomosis
seems to increase the risk of stone formation; in fact, after
surgery we observed a relevant decrease of urinary volume (p
< 0.001), pH (p < 0.0001) and urinary excretion of
citrate (p < 0.0001) as well as magnesium (p < 0.005).
Patients with IBD seem to be at greater risk of stone
formation than patients with idiopathic calcium lithiasis; in
fact, they show a lower excretion of citrate (p < 0.001)
and magnesium (p < 0.001) together with a low urinary pH (p
< 0.001) and volume (p < 0.001). Urinary volume
reduction is probably one of the major risk factors together
with the decrease of small molecular weight inhibitors that is
a constant finding in all patients with IBD.
Calcium and calcium magnesium carbonate specimens
submitted as urinary tract stones
Gault M.H.; Chafe L.; Longerich L.; Mason R.A.
Department of Earth Sciences, Memorial University, General
Hospital, St. John's, Nfld. Canada
J. Urol. (USA), 1993, 149/2 (244-249)
Of 8,129 specimens submitted as urinary stones from 6,095
patients, 67 from 15 patients were predominantly calcium
carbonate or calcium magnesium carbonate (dolomite) by
infrared analysis. Detailed study of 1 man and 4 women who
submitted 3 or more such specimens showed that all were of
aragonite calcium carbonate crystal form in 2 women and all
calcite in the man. All 3 patients had a long history of
nephrolithiasis preceding submission of calcium carbonate
stones. There was frequent and often painful spontaneous
passage of many small stones. Medullary sponge kidney was
reported in 2 patients. Specimens submitted by the other 2
women included dolomite and quartz artifacts. Of the other 10
patients 4 had calcite and 1 had aragonite (possibly true
stones). Five patients had artifacts with dolomite in 3 and
mixed specimens in 2. True calcium carbonate kidney stones and
calcium carbonate artifacts may be difficult to distinguish,
and dolomite and quartz artifacts may require x-ray
diffraction for clear-cut diagnosis.
Etiology and treatment of urolithiasis
Center for Mineral Metabolism and Clinical Research,
University of Texas
Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd,
Dallas, TX 75235-8885 USA
Am. J. Kidney Dis. (USA), 1991, 18/6 (624-637)
Nephrolithiasis is a heterogeneous disorder, with varying
chemical composition and pathophysiologic background. Although
kidney stones are generally composed of calcium oxalate or
calcium phosphate, they may also consist of uric acid,
magnesium-ammonium phosphate, or cystine. Stones develop from
a wide variety of metabolic or environmental disturbances,
including varying forms of hypercalciuria, hypocitraturia,
undue urinary acidity, hyperuricosuria, hyperoxaluria,
infection with urease-producing organisms, and cystinuria. The
cause of stone formation may be ascertained in most patients
using the reliable diagnostic protocols that are available for
the identification of these disturbances. Effective medical
treatments, capable of correcting underlying derangements,
have been formulated. They include sodium cellulose phosphate,
thiazide, and orthophosphate for hypercalciuric
nephrolithiasis; potassium citrate for hypocitraturic calcium
nephrolithiasis; acetohydroxamic acid for infection stones;
and D-penicillamine and alpha-mercaptopropionylglycine for
cystinuria. Using these treatments, new stone formation can
now be prevented in most patients.
Pathogenesis of nephrolithiasis post-partial ileal
bypass surgery: Case-control study
Obialo C.I.; Clayman R.V.; Matts J.P.; Fitch L.L.; Buchwald
H.; Gillis M. ; Hruska K.A.
Renal Division, Jewish Hospital, Washington University School
of Medicine, 216 South Kingshighway Blvd., St. Louis, MO 63110
USA
Kidney Int. (USA), 1991, 39/6 (1249-1254)
Between 1975 and 1983, 838 patients were randomized into
the Program on the Surgical Control of Hyperlipidemias (POSCH)
trial: 417 to standard medical care and 421 to partial ileal
bypass (PIB) surgery. During the course of the trial, an
increased incidence of kidney stone formation was found in the
surgery group (4%/year) as compared to the control group
(0.4%/year). A matched triplet case-control study was
conducted to assess the possible causes for the increased
incidence of kidney stones. Three groups were studied: PIB
stone-formers (S); PIB non-stone formers (N); and non-PIB,
non-stone formers in the control group (C). Initially, 162
patients (54 triplets) were selected. Ten percent of the
patients declined to participate which resulted in a sample
size of 146 patients. The PIB patients had statistically
significant (P < 0.05) lower levels of serum vitamin D
metabolites; lower urine volume, pH, citrate, magnesium,
carbon dioxide, and sulfate, and higher urinary oxalate,
ammonia and relative supersaturation for calcium oxalate and
uric acid than the control patients. Although S and N had
similar results, those S with no prior history of stones had a
higher calcium oxalate supersaturation than similar N with a
negative prior history of stones (P < 0.025). Based on
these results, all PIB patients appear to be at risk for
kidney stone formation. The combination of reduced urinary
volume and calcium oxalate precipitation inhibitor substance
with increased calcium oxalate relative supersaturation
produced an increase in nephrolithiasis risk in the PIB
groups.
The effect of glucose intake on urine saturation
with calcium oxalate, calcium phosphate, uric acid and sodium
urate
Gluszek J.
Department of Internal Diseases, Medical Academy, Poznan
Poland
Int. Urol. Nephrol. (Netherlands), 1988, 20/6
(657-663)
The effect of simple carbohydrate intake on the state of
urine saturation was studied in 44 patients with calcium
kidney stones and in 28 healthy subjects. Renal excretion of
calcium, magnesium and oxalate significantly increased and pH
of urine decreased after an intake of 100 g glucose in stone
formers and healthy subjects. In the basic conditions (before
glucose administration) urine was supersaturated with calcium
oxalate in stone formers (median 0.55) and healthy subjects
(0.24; p < 0.05). Carbohydrate intake caused a significant
increase of the degree of urine saturation with calcium
oxalate and uric acid. The degree of urine saturation with
brushite and sodium urate after glucose administration did not
change. These data suggest that excess of simple carbohydrate
consumption may increase the degree of urine saturation with
some of the compounds important in stone formation.
Magnesium metabolism in health and disease
Elin R.J.
Department of Clinical Pathology, National Institute of
Health, Bethesda, MD
Dis. Mon. (USA), 1988, 34/4 (166-218)
Magnesium is an important element for health and disease.
Magnesium, the second most abundant intracellular cation, has
been identified as a cofactor in over 300 enzymatic reactions
involving energy metabolism and protein and nucleic acid
synthesis. Approximately half of the total magnesium in the
body is present in soft tissue, and the other half in bone.
Less than 1% of the total body magnesium is present in blood.
Nonetheless, the majority of our experimental information
comes from determination of magnesium in serum and red blood
cells. At present, we have little information about
equilibrium among and state of magnesium within body pools.
Magnesium is absorbed uniformly from the small intestine and
the serum concentration controlled by excretion from the
kidney. The clinical laboratory evaluation of magnesium status
is primarily limited to the serum magnesium concentration,
24-hour urinary excretion, and percent retention following
parenteral magnesium. However, results for these tests do not
necessarily correlate with intracellular magnesium. Thus,
there is no readily available test to determine
intracellular/total body magnesium status. Magnesium
deficiency may cause weakness, tremors, seizures, cardiac
arrhythmias, hypokalemia, and hypocalcemia. The causes of
hypomagnesemia are reduced intake (poor nutrition or IV fluids
without magnesium), reduced absorption (chronic diarrhea,
malabsorption, or bypass/resection of bowel), redistribution
(exchange transfusion or acute pancreatitis), and increased
excretion (medication, alcoholism, diabetes mellitus, renal
tubular disorders, hypercalcemia, hyperthyroidism,
aldosteronism, stress, or excessive lactation). A large
segment of the U.S. population may have an inadequate intake
of magnesium and may have a chronic latent magnesium
deficiency that has been linked to atherosclerosis, myocardial
infarction, hypertension, cancer, kidney stones, premenstrual
syndrome, and psychiatric disorders. Hypermagnesemia is
primarily seen in acute and chronic renal failure, and is
treated effectively by dialysis.
Prophylaxis of recurring urinary stones:hard or
soft mineral water
Sommariva M.; Rigatti P.; Viola M.R.
Divisione di Urologia, Ospedale S.Raffaele - 20100 Milano
Italy
Minerva Med. (Italy), 1987, 78/24 (1823-1829)
The influence of a calcium-rich mineral water on urine
crystallisation in patients with recurring kidney stones was
investigated. A calcium and magnesium rich water like the one
tested increases the calcium and magnesium content of the
urine but decreases oxaluria even after a dietary oxalate
load.
Urothelial injury to the rabbit bladder from
various alkaline and acidic solutions used to dissolve kidney
stones
Reckler J.; Rodman J.S.; Jacobs D.; et al.
Division of Urology, Department of Medicine, Cornell
University School of Medicine, New York, NY USA
J. Urol. (Baltimore) (USA), 1986, 136/1
(181-183)
Different irrigating solutions are used clinically to
dissolve uric acid, cystine and struvite stones. These studies
were undertaken to assess the toxicity to the rabbit bladder
epithelium of several commonly used formulations. Test
solutions were infused antegrade through a left ureterotomy
overnight. Bladders were removed and routine histological
sections made. A pH 7.6 solution of NaHCOsub 3 appeared
harmless. The same solution with two percent acetylcysteine
produced slight injury. All pH solutions caused significant
damage to the urothelium. Hemiacidrin, which contains
magnesium, produced less danger than did other pH 4 solutions
without that cation. Our data tend to support Suby's
conclusions that addition of magnesium reduces urothelial
injury even though the presence of magnesium will slow
dissolution of struvite.
Kidney stones, magnesium and spa treatment
Carles J.
Rue des Thermes, 65130 Capvern les Bains France
Presse Therm. Clim. (France), 1983, 120/1
(33-35)
No abstract.
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