Calcium Oxalate Crystalluria and Urine Saturation in Recurrent Renal Stone-Formers

1971 ◽  
Vol 40 (5) ◽  
pp. 365-374 ◽  
Author(s):  
W. G. Robertson ◽  
M. Peacock ◽  
B. E. C. Nordin

1. The degree of saturation with calcium oxalate has been determined in fresh urine samples from six patients with recurrent calcium oxalate-containing renal stones and six normal control subjects who were studied under the same conditions of diet and fluid intake. 2. The degree of saturation of urine with calcium oxalate was significantly higher in the group of stone-formers than in the control series and more often exceeded the amount needed for spontaneous crystallization of calcium oxalate (formation product). This was accounted for by the higher concentration of calcium and oxalate in the urine of the stone-formers. 3. Crystals of calcium oxalate were observed in all freshly examined urines in which the formation product of calcium oxalate was exceeded. Since the formation product of calcium oxalate was exceeded more often in the urines of stone-formers than in the urines of the control subjects, this accounted for the greater calcium oxalate crystalluria of the stone-formers. 4. Addition of a small quantity of sodium oxalate to the basal diets of the two groups resulted in a greater increase in the urine saturation and calcium oxalate crystalluria of the stone-formers, thus accentuating the difference observed between the two groups when they were given the basal diet. 5. Calcium oxalate crystalluria was related quantitatively to the degree of over-saturation of urine with calcium oxalate, although uric acid solubility may play a small role at low pH values. 6. The results are consistent with a ‘hyperexcretion—crystallization’ mechanism of stone formation.

1974 ◽  
Vol 47 (1) ◽  
pp. 13-22 ◽  
Author(s):  
W. G. Robertson ◽  
M. Peacock ◽  
R. W. Marshall ◽  
F. Knowles

1. The volume, size and type of calcium oxalate crystals excreted in the urine of a group of patients with recurrent ‘idiopathic’ stones were studied on a controlled basal diet, after an oral supplement of sodium oxalate and after oral administration of ethane-1-hydroxy-1,1-diphosphonate (EHDP) for 4 weeks. 2. Before administration of EHDP the stone-formers passed the large crystals and aggregates of calcium oxalate dihydrate characteristic of recurrent calcium oxalate stone-formers. For the same level of urine saturation and crystalluria EHDP caused a significant reduction in the proportion of large crystals and aggregates excreted. Studies by light-microscopy confirmed that EHDP caused a striking change in the size and habit of calcium oxalate crystals in some but not all of the urine samples examined. 3. The decrease in average crystal size during the administration of EHDP was attributed to the observed increase in the ability of urine to inhibit the growth and aggregation of calcium oxalate crystals as measured by a growth system in vitro. 4. The possible use of EHDP as a therapeutic agent in the treatment of calcium oxalate stone-formation is discussed.


1972 ◽  
Vol 43 (4) ◽  
pp. 499-506 ◽  
Author(s):  
W. G. Robertson ◽  
M. Peacock

1. The particle size distributions of calcium oxalate crystals were measured at 37°C in fresh urine from recurrent, idiopathic stone-formers and their controls under the same conditions of dietary and fluid intake. The crystals excreted by the controls were small and belonged to a unimodal distribution, whereas those excreted by the stone-formers belonged to a distribution which contained a second peak of much larger particles. The proportion of large crystals in the urines of the stone-formers was significantly higher than in the urines of the controls. 2. The difference in the proportion of large particles passed by the two groups was accentuated by adding a small quantity of sodium oxalate to their diets. Whereas the controls continued to excrete only small crystals of calcium oxalate, the stone-formers passed most of their crystals as large particles. 3. Further investigations showed that the urines of the controls contained a potent inhibitor of the growth and aggregation of calcium oxalate crystals in vitro and that the inhibitor was deficient in the urines of the recurrent stone-formers. 4. It is suggested that the inhibitor in normal urine may allow calcium oxalate to be passed harmlessly in the form of small particles, whereas the lower inhibitory activity in the urines of the recurrent stone-formers is insufficient to prevent the growth of the primary crystals into the large aggregates seen in these urines. By blocking the formation of abnormally large crystals and aggregates the inhibitor may therefore play an important role in preventing crystalluria leading to stone formation.


1977 ◽  
Vol 53 (2) ◽  
pp. 141-148 ◽  
Author(s):  
J. M. Baumann ◽  
S. Bisaz ◽  
R. Felix ◽  
H. Fleisch ◽  
U. Ganz ◽  
...  

1. In order to assess the relative importance of possible pathogenetic factors in the formation of calcium-containing renal stones, a group of 18 patients (12 men, six women) with active, recurrent stone disease were compared with 16 age-matched control subjects (10 men, six women) given an identical diet. 2. Fifteen (83%) of the patients showed at least one, eight (44%) showed two, and one (6%) patient showed three abnormalities that might predispose to stone formation. 3. Increased urinary calcium excretion was the most common abnormality (11 patients, 61%), particularly in the women (83%). 4. A diminished excretion of inhibitors of crystal formation of calcium phosphate was the next most common abnormality, which occurred in eight patients (44%), all of whom were men. It was largely attributable to a diminished excretion of inorganic pyrophosphate (PPi). The PPi/orthophosphate ratios were also lower in the stone-formers. Significant differences in residual inhibitory activity after enzymatic removal of PPi between control subjects and stone-formers could not be found in 24 h urine samples but were present during certain times of the day. Pyrophosphate showed a higher inhibitory activity in urine than in control solutions, this enhancement being absent in stone-formers. 5. Nine (50%) of the patients, but only one of the control subjects, produced crystal aggregates greater than 50 μm in diameter after an oral load of oxalate.


1994 ◽  
Vol 86 (3) ◽  
pp. 239-243 ◽  
Author(s):  
Bruno Baggio ◽  
Giovanni Gambaro ◽  
Francesco Marchini ◽  
Massimo Vincenti ◽  
Giulio Ceolotto ◽  
...  

1. Anomalous transmembrane anion transport has been observed in erythrocytes of patients with idiopathic calcium nephrolithiasis. 2. To verify whether cation transport is also abnormal, we investigated the frusemide-sensitive Na+ efflux from Na+-loaded erythrocytes and the natriuretic response to acute intravenous frusemide administration in calcium oxalate renal stone formers. 3. Frusemide administration induced a statistically significant smaller increase in the fractional excretion of Na+ in patients than in control subjects. Abnormal kinetic properties of erythrocyte Na+-K+-2Cl− co-transport were observed in approximately 60% of stone formers. The Km for Na+ of Na+-K+-2Cl− co-transport correlated with urinary Ca2+ excretion. 4. The abnormal kinetic properties of Na+-K+-2Cl− co-transport may be relevant for stone formation, hampering renal Ca2+ reabsorption in the distal nephron and determining critical physicochemical conditions for calcium/oxalate crystallization.


Kidney360 ◽  
2020 ◽  
pp. 10.34067/KID.0006942020
Author(s):  
Jessica J. Saw ◽  
Mayandi Sivaguru ◽  
Elena M. Wilson ◽  
Yiran Dong ◽  
Robert A. Sanford ◽  
...  

Background: Human kidney stones form via repeated events of mineral precipitation, partial dissolution and reprecipitation, which are directly analogous to similar processes in other natural and man-made environments where resident microbiomes strongly influence biomineralization. High-resolution microscopy and high-fidelity metagenomic (microscopy-to-omics) analyses, applicable to all forms of biomineralization, have been applied to assemble definitive evidence of in vivo microbiome entombment during urolithiasis. Methods: Stone fragments were collected from a randomly chosen cohort of 20 patients using standard percutaneous nephrolithotomy (PCNL). Fourier transform infrared (FTIR) spectroscopy indicated that 18 of these patients were calcium oxalate (CaOx) stone formers, while one patient each formed brushite and struvite stones. This apportionment is consistent with global stone mineralogy distributions. Stone fragments from 7 of these 20 patients (5 CaOx, 1 brushite and 1 struvite) were thin sectioned and analyzed using brightfield (BF), polarization (POL), confocal, superresolution autofluorescence (SRAF) and Raman techniques. DNA from remaining fragments, grouped according to each of the 20 patients, were analyzed with amplicon sequencing of 16S rRNA gene sequences (V1-V3, V3-V5) and internal transcribed spacer (ITS1, ITS2) regions. Results: Bulk entombed DNA was sequenced from stone fragments in 11 of the 18 CaOx patients, as well as the brushite and struvite patients. These analyses confirmed the presence of an entombed low-diversity community of bacteria and fungi, including Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Aspergillus niger. Bacterial cells ~1  µm in diameter were also optically observed to be entombed and well-preserved in amorphous hydroxyapatite spherules and fans of needle-like crystals of brushite and struvite. Conclusions: These results indicate a microbiome is entombed during in vivo CaOx stone formation. Similar processes are implied for brushite and struvite stones. This evidence lays the groundwork for future in vitro and in vivo experimentation to determine how the microbiome may actively and/or passively influence kidney stone biomineralization.


1994 ◽  
Vol 40 (9) ◽  
pp. 1739-1743 ◽  
Author(s):  
R Knörle ◽  
P Schnierle ◽  
A Koch ◽  
N P Buchholz ◽  
F Hering ◽  
...  

Abstract Tamm-Horsfall glycoprotein (THP) from healthy probands inhibits the precipitation of calcium oxalate, whereas THP from individuals who repeatedly develop calcium oxalate stones has no effect or even promotes precipitation. Using Fourier-transform infrared spectroscopy, we found a structural differentiation between these functionally different THPs: a decisive difference in sialic acid content. Quantitative analysis for sialic acid showed the same results. THP from healthy probands had a high sialic acid content (51 +/- 9 g/kg), whereas THP from recurrent stone formers had a decreased sialic acid content (21 +/- 4 g/kg). This explains the dual role of THP in the precipitation of calcium oxalate and the formation of renal stones and shows the importance of glycosylation in the function of this glycoprotein.


1990 ◽  
Vol 79 (2) ◽  
pp. 113-116 ◽  
Author(s):  
Bruno Baggio ◽  
Giovanni Marzaro ◽  
Giovanni Gambaro ◽  
Francesco Marchini ◽  
Hibbard E. Williams ◽  
...  

1. This study was performed to test the hypothesis that glycosaminoglycans may play an important role in the observed abnormalities in oxalate flux seen in patients with calcium oxalate nephrolithiasis. 2. Oxalate flux rate, erythrocyte membrane glycosaminoglycan content, membrane protein phosphorylation and effect of heparan sulphate on erythrocyte oxalate flux in vitro were studied in control subjects and patients with calcium oxalate nephrolithiasis. 3. In comparison with control subjects, renal stone-formers showed a significantly higher oxalate self-exchange, a lower erythrocyte membrane glycosaminoglycan content and a higher membrane phosphorylation rate. In stone-formers, erythrocyte glycosaminoglycan content correlated inversely with both oxalate flux rate and protein phosphorylation. In vitro, heparan sulphate promoted a significant fall in the rate of oxalate self-exchange. 4. These findings support the hypothesis that a lower erythrocyte membrane content of glycosaminoglycans enhances membrane protein phosphorylation, leading to an increased rate of transmembrane oxalate flux.


1989 ◽  
Vol 257 (1) ◽  
pp. F99-F106 ◽  
Author(s):  
B. Hess ◽  
Y. Nakagawa ◽  
F. L. Coe

Normal urine inhibits both the growth and the aggregation of calcium oxalate monohydrate (COM) crystals but the molecules that inhibit aggregation are not well defined. We have developed a spectrophotometric assay method to measure the aggregation of COM crystals in vitro under conditions that avoid simultaneous crystal growth. At pH 7.2 and 90 mM NaCl, Tamm-Horsfall glycoprotein (THP) and nephrocalcin (NC), a major urinary inhibitor of COM crystal growth, inhibit COM crystal aggregation at concentrations as low as 2 X 10(-9) and 1 X 10(-8) M, respectively. When increasing NaCl to 270 mM or lowering pH to 5.7, inhibition by both glycoproteins, but more markedly by THP, is decreased. Urinary NC from calcium oxalate renal stone formers (SF NC) and NC isolated from calcium oxalate renal stones (stone NC) both inhibit COM crystal aggregation 10-fold less than NC from normal urine. Citrate is ineffective even at millimolar concentrations. Thus THP and NC are two major inhibitors of COM crystal aggregation in normal urine; SF NC and stone NC are defective aggregation inhibitors.


2013 ◽  
Vol 12 (3) ◽  
pp. 85-86
Author(s):  
S. Oehlschläger ◽  
T. Muck ◽  
B. Hager ◽  
S. Füssel ◽  
M.P. Wirth

1975 ◽  
Vol 49 (6) ◽  
pp. 597-602 ◽  
Author(s):  
W. G. Robertson ◽  
M. Peacock ◽  
R. W. Marshall ◽  
R. Speed ◽  
B. E. C. Nordin

1. A retrospective cross-sectional study was carried out on data derived from single 24 h urine collections from 246 male idiopathic calcium stone-formers. 2. The daily urine volume and pH and the excretions of calcium, oxalate, phosphate, creatinine and magnesium were related to the time of year when the urine was collected, and the saturation of urine with calcium oxalate and octocalcium phosphate calculated for each month. 3. There were significant seasonal variations in the urinary excretion of calcium and oxalate, each showing a maximum during the summer months and a minimum in the winter. There was no significant seasonal variation in urinary pH, volume, creatinine, phosphate or magnesium. 4. There was a significant increase in the saturation of urine with calcium oxalate and a trend towards higher saturation levels of octo-calcium phosphate in the summer. These changes were dependent only on the seasonal variation in urinary calcium and oxalate and not on urine volume. 5. A retrospective study of the seasonal incidence of stone episodes among these 246 stone-formers showed that the rate of stone passage per month was 50% higher in the summer than in the winter. There was no significant seasonal variation in the incidence of stones removed surgically.


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