Ita Pfeferman Heilberg

Influence of Muscle Mass and Physical Activity on Serum and Urinary Creatinine and Serum Cystatin C

BACKGROUND AND OBJECTIVES For addressing the influence of muscle mass on serum and urinary creatinine and serum cystatin C, body composition was assessed by skinfold thickness measurement and bioelectrical impedance analyses. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 170 healthy individuals (92 women, 78 men) were classified as sedentary or with mild or moderate/intense physical activity. Blood, 24-h urine samples, and 24-h food recall were obtained from all individuals. RESULTS Serum and urinary creatinine correlated significantly with body weight, but the level of correlation with lean mass was even greater. There was no significant correlation between body weight and lean mass with cystatin C. Individuals with moderate/intense physical activity presented significantly lower mean body mass index (23.1 +/- 2.5 versus 25.7 +/- 3.9 kg/m(2)) and higher lean mass (55.3 +/- 10.0 versus 48.5 +/- 10.4%), serum creatinine (1.04 +/- 0.12 versus 0.95 +/- 0.17 mg/dl), urinary creatinine (1437 +/- 471 versus 1231 +/- 430 mg/24 h), protein intake (1.4 +/- 0.6 versus 1.1 +/- 0.6 g/kg per d), and meat intake (0.7 +/- 0.3 versus 0.5 +/- 0.4 g/kg per d) than the sedentary individuals. Conversely, mean serum cystatin did not differ between these two groups. A multivariate analysis of covariance showed that lean mass was significantly related to serum and urinary creatinine but not with cystatin, even after adjustment for protein/meat intake and physical activity. CONCLUSIONS Cystatin C may represent a more adequate alternative to assess renal function in individuals with higher muscle mass when mild kidney impairment is suspected.

Abordagem diagnóstica e terapêutica na infecção do trato urinário: ITU

A review about recent aspects on diagnosis and clinical management of urinary tract infection (UTI) is presented. There is a wide variation in clinical presentation of UTI which include different forms as cystitis, pyelonephritis, urethral syndrome and the clinical relevance of asymptomatic bacteriuria and low-count bacteriuria that must be distinguished from contamination. Pathogenetic aspects concerning bacterial virulence as well as host factors in susceptibility to UTI as urinary tract obstruction, vesicoureteral reflux, indwelling bladder catheters, pregnancy, diabetes mellitus, sexual activity, contraceptive methods, prostatism, menopause, advanced age and renal transplantation are discussed. Diagnostic criteria and the most common tests utilized for differentiation between lower and upper UTI have been reviewed. The authors conclude that a careful evaluation of the underlying factors is required for the correct diagnosis of UTI and to prevent recurrence and that appropriate strategies and specific therapeutic regimens may maximize the benefit while reducing costs and adverse reactions.

Bone disease in idiopathic hypercalciuria.

Purpose of reviewDecreased bone mineral density and increased prevalence of bone fractures have been found in patients with idiopathic hypercalciuria. The purpose of this review is to summarize the recent published evidence that supports a potential role of the bone, and its link to the kidney and intestine, in the pathogenesis of idiopathic hypercalciuria. The effects of hypercalciuria on bone and the implications for treatment are also reviewed. Recent findingsEvidence suggests that the incidence of a first fracture in kidney stone patients is fourfold higher than the control population. Support for the role of bone in the pathophysiology of hypercalciuria has been corroborated. New studies have detailed the effects of several cytokines – increased number and sensitivity of vitamin D receptors, and increased acid production – upon the bone acting cells. Similarly, recent clinical and experimental studies have suggested that genetic factors confer a predisposition to the formation of renal calcium stones and bone demineralization. SummaryWhether hypercalciuria is the result of a primary bone disorder, a consequence of a persisting negative calcium balance or a combination of both still remains to be determined. Nevertheless, bone status must be evaluated and followed up in patients with idiopathic hypercalciuria.

Renal stone disease: causes, evaluation and medical treatment

The purpose of the present review is to provide an update about the most common risk factors or medical conditions associated with renal stone formation, the current methods available for metabolic investigation, dietary recommendations and medical treatment. Laboratory investigation of hypercalciuria, hyperuricosuria, hyperoxaluria, cystinuria, hypocitraturia, renal tubular acidosis, urinary tract infection and reduction of urinary volume is based on the results of 24-hr urine collection and a spot urine for urinary sediment, culture and pH. Blood analysis for creatinine, calcium and uric acid must be obtained. Bone mineral density has to be determined mainly among hypercalciurics and primary hyperparathyroidism has to be ruled out. Current knowledge does not support calcium restriction recommendation because it can lead to secondary hyperoxaluria and bone demineralization. Reduction of animal protein and salt intake, higher fluid intake and potassium consumption should be implemented. Medical treatments involve the use of thiazides, allopurinol, potassium citrate or other drugs according to the metabolic disturbances. The correction of those metabolic abnormalities is the basic tool for prevention or reduction of recurrent stone formation.

Estrogen Receptor (ER) Gene Polymorphism May Predict the Bone Mineral Density Response to Raloxifene in Postmenopausal Women on Chronic Hemodialysis

The estrogen receptor (ER) gene has been considered as a candidate genetic marker for osteoporosis, and PvuII and XbaI polymorphisms of the ERα gene have been associated with low bone mineral density (BMD). We investigated whether ER polymorphism could predict the response of BMD in 28 postmenopausal women on hemodialysis with marked osteopenia or osteoporosis, randomized to receive raloxifene, a selective estrogen receptor modulator (SERM), or placebo for 1 year. BMD was assessed by dual X-ray absorptiometry and PvuII and XbaI restriction fragment-length polymorphism of the ER gene was determined using polymerase chain reaction. Baseline lumbar spine or femoral neck BMD parameters were not different between patients presenting either homozygous PP or xx when compared with heterozygous Pp or Xx genotypes. After 1 year, patients on raloxifene, presenting with PP or xx genotypes (but not those with Pp or Xx), showed a significantly higher mean lumbar spine BMD (0.942 ± 0.18 vs. 0.925 ± 0.17 g/cm2, p < .01) and lower serum pyridinoline (19.7 ± 9.7 vs. 30.6 ± 16.5 nmol/L, p < .02) when compared with baseline values. No changes were detected in the placebo-treated patients or in the femur neck sites. In conclusion, after 1 year on raloxifene, postmenopausal osteoporotic women on chronic hemodialysis, homozygous for the P or x (PP or xx) alleles of the ER, exhibited a better lumbar spine BMD response and decreased serum pyridinoline values when compared with heterozygous women (Pp or Xx), suggesting that ERα allelic variants may explain, at least in part, the different outcomes after treatment of osteoporosis with SERM.

Evaluation of nephrolithiasis in autosomal dominant polycystic kidney disease patients.

BACKGROUND AND OBJECTIVES Nephrolithiasis (LIT) is more prevalent in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. Renal ultrasonography may underdetect renal stones because of difficulties imposed by parenchymal and/or cyst wall calcifications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 125 patients with ADPKD underwent ultrasonography and unenhanced computed tomography (CT) scan, routine blood chemistry, and spot and 24-h urine collections. RESULTS CT scan detected calculi in 32 patients, including 20 whose previous ultrasonography revealed no calculi. The percentage of hypocitraturia was high but not statistically different between patients with ADPKD+LIT or ADPKD. Hyperuricosuria and distal renal tubular acidosis were less prevalent but also did not differ between groups, whereas hyperoxaluria was significantly higher in the former. Hypercalciuria was not detected. Renal volume was significantly higher in patients with ADPKD+LIT versus ADPKD, and a stepwise multivariate logistic regression analysis showed that a renal volume >or=500 ml was a significant predictor of LIT in patients with ADPKD and normal renal function, after adjustments for age and hypertension. CONCLUSIONS CT scan was better than ultrasonography to detect LIT in patients with ADPKD. Larger kidneys from patients with ADPKD were more prone to develop stones, irrespective of the presence of metabolic disturbances.

Response to Dietary Oxalate after Bariatric Surgery

BACKGROUND AND OBJECTIVES Bariatric surgery (BS) may be associated with increased oxalate excretion and a higher risk of nephrolithiasis. This study aimed to investigate urinary abnormalities and responses to an acute oxalate load as an indirect assessment of the intestinal absorption of oxalate in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Twenty-four-hour urine specimens were collected from 61 patients a median of 48 months after BS (post-BS) as well as from 30 morbidly obese (MO) participants; dietary information was obtained through 24-hour food recalls. An oral oxalate load test (OLT), consisting of 2-hour urine samples after overnight fasting and 2, 4, and 6 hours after consuming 375 mg of oxalate (spinach juice), was performed on 21 MO and 22 post-BS patients 12 months after BS. Ten post-BS patients also underwent OLT before surgery (pre-BS). RESULTS There was a higher percentage of low urinary volume (<1.5 L/d) in post-BS versus MO (P<0.001). Hypocitraturia and hyperoxaluria (P=0.13 and P=0.36, respectively) were more frequent in BS versus MO patients. The OLT showed intragroup (P<0.001 for all periods versus baseline) and intergroup differences (P<0.001 for post-BS versus MO; P=0.03 for post-BS versus pre-BS). The total mean increment in oxaluria after 6 hours of load, expressed as area under the curve, was higher in both post-BS versus MO and in post-BS versus pre-BS participants (P<0.001 for both). CONCLUSIONS The mean oxaluric response to an oxalate load is markedly elevated in post-bariatric surgery patients, suggesting that increased intestinal absorption of dietary oxalate is a predisposing mechanism for enteric hyperoxaluria.

Effect of Etidronate Treatment on Bone Mass of Male Nephrolithiasis Patients with Idiopathic Hypercalciuria and Osteopenia

Osteopenia is frequently found among calcium stone forming (CSF) patients with hypercalciuria. We investigated the effect of a 2-year therapeutic course of etidronate, a bone-sparing agent, in 7 young male CSF patients. The treatment consisted of a cyclic intermittent administration of phosphate followed by sodium etidronate and calcium supplementation every 74 days. Bone mineral density (BMD) measured at 12-month intervals and bone biopsies performed at baseline and after 2 years were the primary efficacy parameters. Mean lumbar spine BMD increased significantly after the 1st year by 2.6 ± 1.0% (mean ± SE, p < 0.05) and nonsignificantly after the 2nd year by 5.6 ± 2.6%. Nonsignificant changes were observed for femoral neck mean BMD after either the 1st or the 2nd year (decrease of 2.0 ± 1.0% and 2.0 ± 3.0%, respectively). Mean histomorphometric parameters showed that bone volume, osteoid volume, and eroded surfaces did not differ from baseline (13.9 ± 2.2 vs. 12.2 ± 1.1%, 1.2 ± 0.7 vs. 2.6 ± 0.7%, and 20.7 ± 6.2 vs. 13.7 ± 1.3%, respectively). Osteoid surface was significantly lower than baseline values (9.5 ± 5.2 vs. 18.8 ± 5.3%, p < 0.05). These data suggest that etidronate given to young male CSF patients presenting with hypercalciuria and osteopenia led to a significant amelioration of BMD, evident only in the lumbar spine after 1 year of treatment. There was no histological evidence of long-term improvement in bone remodeling.

Phyllanthus niruri as a Promising Alternative Treatment for Nephrolithiasis

In spite of considerable efforts to identify effective treatments for urolithiasis, this is a goal yet to be achieved. This review summarizes experimental and clinical data evaluating the effect of the plant Phyllanthus niruri, a plant with worldwide distribution, as a potential agent to prevent and/or to treat urolithiasis The review is based on data from the literature and on the results obtained by our group from either in vivo/in vitro experiments or clinical studies. Phyllanthus niruri has been shown to interfere with many stages of stone formation, reducing crystals aggregation, modifying their structure and composition as well as altering the interaction of the crystals with tubular cells leading to reduced subsequent endocytosis. The clinical beneficial effects of Phyllanthus niruri may be related to ureteral relaxation, helping to eliminate calculi or to clear fragments following lithotripsy, or also to a putative reduction of the excretion of urinary crystallization promoters such as calcium. No adverse renal, cardiovascular, neurological or toxic effects have been detected in either of these studies. Altogether, these studies suggest a preventive effect of Phyllanthus niruri in stone formation or elimination, but still longer-term randomized clinical trials are necessary to confirm its therapeutic properties.

Vitamin D receptor gene polymorphism and bone mineral density in hypercalciuric calcium-stone-forming patients.

Reduced bone mineral density (BMD) and an increased risk of vertebral fracture have been reported in calcium-stone-forming (CSF) patients presenting with idiopathic hypercalciuria. We investigated the association between BsmI vitamin D receptor (VDR) polymorphism and BMD in 68 hypercalciuric CSF patients (35 males and 33 premenopausal females, mean age ± SD = 39 ± 10 years). BMD was measured at lumbar spine (L2–L4) and femur neck sites using dual energy X-ray absorptiometry. A 72-hour dietary record and a 24-hour urine sample were obtained from each patient to determine calcium intake and excretion. The allelic frequency found for the sample as a whole was 16% BB, 44% Bb and 40% bb. Mean BMD values did not significantly differ among BB, Bb and bb patients at L2–L4 (1.162 ± 0.10, 1.133 ± 0.11 and 1.194 ± 0.19 g/cm2, mean ± SD, respectively) or at neck sites (0.920 ± 0.11, 0.931 ± 0.15 and 0.982 ± 0.15 g/cm2, respectively). Calcium intake and excretion were also not significantly different among the three genotypes. Patients were then divided into two groups, normal BMD, T-score ≧–1 (n = 34) and low BMD, T-score <–1 (n = 34), to further evaluate the allele influence on previous bone loss. Despite a trend for a higher mean BMD at spine or neck sites for patients with one or two b alleles when compared to BB patients, the difference did not reach statistical significance. The distribution of BB, Bb and bb genotypes in the low-bone-mass group (15, 47 and 38%, respectively) was similar to that in the normal-bone-mass group (18, 41 and 14%, respectively). These data suggest that BsmI VDR polymorphism does not play an important role in the bone loss seen in hypercalciuric CSF patients.