Calcium decreases urinary oxalate

The effects of calcium supplementation on urinary oxalate excretion was tested in 9 normal subjects, 4 males and 5 females between 23 and 49 years of age. In a crossover study 800 mg calcium was orally administered as active absorbable algal calcium (AAACa) (A) and calcium carbonate (B), and compared with non-calcium containing placebo (C). Calcium, oxalate, osmolality, creatinine and pH were measured in the first three morning urine samples and Ca/osmolality, Ca/osmolality/body weight, Ca/creatinine and oxalate/osmolality were calculated to correct for urine dilution. Ca x oxalate product was also calculated and Ca oxalate crystal in the sediment was microscopically examined and semiquantitatively estimated as -, +, ++, and +++ expressed as 0, 1, 2 and 3 respectively. Urinary Ca excretion was similar in A and B, but significantly larger than C, regardless of the method of correction for dilution. Urinary oxalate excretion tended to be lower in A than in B and C. Urine pH was similar among all three groups. Ca x oxalate product was higher in C than in A and B. AAACa, unlike calcium carbonate, appeared to decrease urinary oxalate excretion and Ca x oxalate product more efficiently than Ca carbonate, suggesting a possibility of inhibiting the formation of Ca x oxalate kidney stones. Formation of calcium oxalate was also tested in vitro by adding oxalate to urine samples and aqueous calcium solution.     

Molecular modulation of calcium oxalate crystallization by osteopontin and citrate

Calcium oxalate monohydrate (COM), which plays a functional role in plant physiology, is a source of chronic human disease, forming the major inorganic component of kidney stones. Understanding molecular mechanisms of biological control over COM crystallization is central to development of effective stone disease therapies and can help define general strategies for synthesizing biologically inspired materials. To date, research on COM modification by proteins and small molecules has not resolved the molecular-scale control mechanisms. Moreover, because proteins directing COM inhibition have been identified and sequenced, they provide a basis for general physiochemical investigations of biomineralization. Here, we report molecular-scale views of COM modulation by two urinary constituents, the protein osteopontin and citrate, a common therapeutic agent. Combining force microscopy with molecular modeling, we show that each controls growth habit and kinetics by pinning step motion on different faces through specific interactions in which both size and structure determine the effectiveness. Moreover, the results suggest potential for additive effects of simultaneous action by both modifiers to inhibit the overall growth of the crystal and demonstrate the utility of combining molecular imaging and modeling tools for understanding events underlying aberrant crystallization in disease.     

Reduction of urinary kallikrein in hypertensive diabetics

Renal Kallikrein, an enzyme of the distal tubule acting through kinin liberation, may participate to the control of renal circulation and blood pressure. To study if an impairment of its secretion may exist in diabetics, a cross-sectional study was carried out on 40 non-hypertensive and 29 hypertensive diabetics, compared to 30-age related controls. Urinary Kallikrein Activity (UKA) was measured by its kininogenase activity with and without trypsin preincubation. Compared to UKA in controls (86 +/- 9 micrograms lysyl-bradykinin [LBK] produced per minute of incubation), UKA was significantly reduced either in non-hypertensive diabetics (59 +/- 8 micrograms LBK. min.-1; p less than 0.05) and in hypertensive diabetics (26 +/- 6 micrograms LBK. min.-1; p less than 0.001). The ratio of total/active urinary kallikrein was similar in diabetics and in controls. The decline of UKA in diabetics was related to the duration of their disease (r = -0.38; p less than 0.05) and to their stage of retinopathy (r = -0.46; p less than 0.001). UKA values were proportional to creatinine clearance in diabetics (r = 0.58; p less than 0.001). The lowest UKA values were found in patients with a high urinary excretion of albumin (above 500 mg/day): 8 +/- 2 micrograms LBK. min-1 (p less than 0.001) and beta-2-microglobulin (above 382 micrograms/day): 12 +/- 4 micrograms LBK. min-1 (p less than 0.001). These findings support that an impaired secretion of renal kallikrein in diabetics can be related to the duration of diabetes and to the severity of microangiopathy.     

Successful treatment of hyperuricosuric calcium oxalate nephrolithiasis with potassium citrate

Calcium stone (renal) formation in patients with hyperuricosuria has been ascribed to the urate-induced crystallization of calcium oxalate. Citrate (0.5mM), added to synthetic medium metastably supersaturated with respect to calcium oxalate, was shown to inhibit heterogeneous nucleation of calcium oxalate by monosodium urate (2 mg/mL). Long-term trial with potassium citrate (60 to 80 mEq/day) was therefore undertaken to determine whether induced hypercitraturia would prevent calcium oxalate stone formation in 19 patients with hyperuricosuria. The treatment produced a sustained rise in urinary pH by 0.55 to 0.85 to the high normal range (6.5 to 7.0). Urinary citrate levels rose by 249 to 402 mg/day to approximate the normal mean value of 643 mg/day. Commensurate with these changes, urinary saturation of calcium oxalate (relative saturation ratio) and the amount of undissociated uric acid declined significantly. However, the urinary uric acid and saturation of monosodium urate remained elevated. Stone formation declined from 1.55 +/- 2.70 per patient-year to 0.38 +/- 1.22 per patient-year during mean treatment period of 2.35 +/- 0.88 years. Stones ceased to form in 16 of 19 patients during treatment. The results provide physicochemical and clinical evidence for the utility of potassium citrate in the management of hyperuricosuric calcium oxalate nephrolithiasis.     

Normalization of urinary oxalate by taurine in glycolate-fed rats

Oral feeding of sodium glycolate (50 mg/d/rat for ten days) caused a significant (P less than 0.001) increase in oxalate and taurine excretion and a decrease in liver protein content (P less than 0.05), glycolic acid oxidase levels (P less than 0.01), and glycolic acid dehydrogenase levels (P less than 0.01) as compared to normal untreated rats. Taurine (100 mg/d/rat), when administered along with glycolate, prevented these effects of glycolate as evident from normal urinary excretion of oxalate, liver protein content, glycolic acid oxidase, and glycolic acid dehydrogenase levels in glycolate- plus taurine-fed animals.     

Serum or urinary concentration of type IV collagen in diabetics

Concentrations of serum or urinary type IV collagen, determined by sandwich enzyme immunoassay, were significantly elevated in diabetics compared to controls (P<.01). Serum or urinary levels of type IV collagen were significantly increased in patients with microangiopathy compared to those without microvascular disease (P < .05). Serum type IV collagen levels were also augmented in diabetics who showed an increased albumin index for 1 year. Serum levels of type IV collagen were not affected by any conditions of metabolic control.The measurement of serum or urinary type IV collagen may be a useful indicator for monitoring the development of diabetic microangiopathy, especially in early diabetic nephropathy.     

Risk factors for the formation of urinary calcium-containing stones in diabetics

Levels of 24-hour urinary calcium, magnesium, oxalate, citrate, uric acid, phosphorus and creatinine as well as urinary volume were determined in 85 patients and 81 normal subjects. Among the patients, 43 were diabetics without stone, 5 diabetics with stone and 37 with idiopathic calcium stone formation in the urinary tract. It is shown that the main risk factors involved in urinary calcium-containing stone formation are the levels of calcium, oxalate, uric acid and citrate and the volume of 24-hour urine. With the data obtained, the authors calculated the ion-activity products index of calcium oxalate and the relative probability of stone formation in the three groups of patients and the control group of normal subjects. The index in normal subjects, diabetics without stone, diabetics with stone and patients with idiopathic urinary calcium stone was 3.07 +/- 0.16, 2.90 +/- 0.25, 3.90 +/- 0.58 and 5.11 +/- 0.38 respectively. The upper limit of the relative probability in normal subjects was 0.54. Most of the patients with idiopathic urinary calcium stone (32/37) and all the 5 diabetics with stone had higher probability value than this, while most of the normal subjects (73/81) and of the diabetics without stone (39/43) had value lower than this. The results indicate that though the diabetics have higher level of urinary calcium and higher value of the product of calcium x oxalate x uric acid, they have also inhibitive factors for stone formation, such as increased level of urinary citrate. As a result, urinary stone formation will not be a frequent occurrence.     

Idiopathic calcium oxalate urinary lithiasis: new physiopathological approaches

Nephrolithiasis effects 1% to 5% of the general population in industrialized countries. The majority of stones is made of calcium oxalate. The formation of calcium oxalate nephrolithiasis depends on several factors: hypercalciuria, hyperoxaluria, adhesion of crystals on the surface of renal epithelial cells, quantitative or qualitative deficit of inhibitors of crystallization in urine, intervention of promotors of crystallization. In this review we report the new insights into calcium oxalate stone formation.     

Intravenous insulin decreases urinary albumin excretion in long-term diabetics with nephropathy

Summary The effect of intravenous injection of insulin on heart rate, plasma noradrenaline and urinary excretion rates of albumin and beta-2-microglobulin was examined in 10 long-term diabetics, 5 of whom had albuminuria. — In patients without albuminuria intravenous injection of insulin resulted in changes similar to but less pronounced than those previously observed in short-term diabetics: albumin excretion, plasma noradrenaline and heart rate increased, creatinine excretion decreased significantly. —Intravenous injection of insulin increased heart rate but not plasma noradrenaline in long-term diabetics with albuminuria. Arterial blood pressure did not change after insulin. Contrary to expectation insulin decreased urinary albumin excretion (from 418 to 312 g/min, 27 per cent) in these patients. There was a marked decrease in urinary excretion rates of beta-2-microglobulin and creatinine (55 and 17 per cent, respectively) after insulin. — The decrease in albumin excretion after insulin in diabetics with albuminuria is most likely due to renal vasoconstriction. The absence of a rise in albumin excretion after insulin may be due to severe morphological changes in glomeruli in these patients.     

Adhesion at calcium oxalate crystal surfaces and the effect of urinary constituents

Kidney stones, aggregates of microcrystals, most commonly contain calcium oxalate monohydrate (COM) as the primary constituent. The aggregation of COM microcrystals and their attachment to epithelial cells are thought to involve adhesion at COM crystal surfaces, mediated by anionic molecules or urinary macromolecules. Identification of the most important functional group-crystal face adhesive combinations is crucial to understanding the stability of COM aggregates and the strength of their attachments to epithelial cell surfaces under flow in the renal tubules of the kidney. Here, we describe direct measurements of adhesion forces, by atomic force microscopy, between various functional groups and select faces of COM crystals immersed in aqueous media. Tip-immobilized carboxylate and amidinium groups displayed the largest adhesion forces, and the adhesive strength of the COM crystal faces decreased in the order (100) > (121) > (010), demonstrating that adhesion is sensitive to the structure and composition of crystal faces. The influence of citrate and certain urinary proteins on adhesion was examined, and it was curious that osteopontin, a suspected regulator of stone formation, increased the adhesion force between a carboxylate tip and the (100) crystal face. This behavior was unique among the various combinations of additives and COM crystal faces examined here. Collectively, the force measurements demonstrate that adhesion of functional groups and binding of soluble additives, including urinary macromolecules, to COM crystal surfaces are highly specific in nature, suggesting a path toward a better understanding of kidney stone disease and the eventual design of therapeutic agents.     

The relationship between autonomic neuropathy and urinary sodium and albumin excretion in insulin-treated diabetics

There is evidence to suggest that renal function may alter in the presence of autonomic neuropathy. Albumin excretion rate (AER) and sodium excretion rate (NaER) in timed daytime (erect) and night-time (supine) urine collections were assessed in 20 insulin-treated diabetics with and in 20 without established autonomic neuropathy, matched for age, sex, duration of diabetes, diabetic control, and systolic blood pressure. All patients were free of proteinuria on albustix testing and had normal serum levels of urea and creatinine. AER based on daytime and pooled 24-hour collections was higher, but not significantly so, in the group with autonomic neuropathy. The nocturnal AER on the other hand was significantly elevated in the group with autonomic neuropathy (p less than 0.02) as was the nocturnal urine volume (p less than 0.01) and sodium excretion rate (p less than 0.05). The corrected nocturnal albumin/creatinine ratio was likewise greater in this group (p less than 0.02). These findings suggest that autonomic neuropathy can independently affect renal function and that nocturnal renal haemodynamics and glomerulotubular balance may be deranged in insulin-treated diabetics with autonomic neuropathy.     

Clinical significance of determination of urinary albumin, beta 2 microglobulin and Tamm-Horsfall protein in diabetics

Twenty-four hour urinary albumin (Alb) beta 2 microglobulin (beta 2m) and Tamm-Horsfall protein (THP) were measured by radioimmunoassay in 69 diabetics and 23 normal controls. The excretion of urinary Alb, beta 2m and THP in the patients with diabetic nephropathy was found to be different from that of normal controls. The abnormality of excretion of Alb, beta 2m and THP is particularly evident in the patients with clinical diabetic nephropathy. These results indicate that the renal lesions of diabetes mellitus exist not only in the glomeruli but also in the proximal and/or distal tubules. There was a significantly positive correlation between THP excretion and creatinine clearance (less than 127 ml/min/1.73m2). The findings suggest that the excretion of urinary THP is a valuable index for evaluating the damages of nephrons. It is believed that determination of urinary Alb, beta 2m and THP in diabetics is beneficial to early detection of the sites and degree of the renal lesions.     

Short-term nalidixic acid plus sodium citrate in acute lower urinary tract infection

Low-dose nalidixic acid (0.66 g) in combination with 4 g of sodium citrate (NAC) was evaluated in acute lower UTI. In college-age females (n = 24) given NAC every 8 h for 3 days the nalidixic acid (NA) susceptible infecting strain was eradicated in 100% of the patients and recurrence during the 1 month follow-up period occurred in 1 case (5%) classified as relapse. In a following study the corresponding rates in general practice (GP) patients (n = 71) were 90% and 17%, respectively, irrespective of treatment with NAC every 12 h for 3 days or 5 days. The failures observed in GP were due to persistence of (or immediate reinfection by) the original infecting strain (4%) or its NA resistant mutant (6%). Emergence of NA resistance was associated with high age of the patient and a high incidence of NA resistant mutants in the infecting Escherichia coli strain. NA susceptible failure and recurrence during follow-up occurred primarily in younger GP patients. The recurrences were equally often classified as relapse (6 cases) as reinfection (5 cases). About 20% of the patients reported rather innocuous transient side effects of NAC and interruption of medication occurred in 1 case (0.6%).