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Aims: Preventing kidney stone recurrence relies on detecting and modifying urine chemistry abnormalities. The assumption is that an abnormality is due to a global metabolic defect present in both kidneys. However, we hypothesize that clinically significant unilateral defects may exist. We aimed to identify these patients by sampling urine from each renal unit., Materials and Methods: Adults undergoing retrograde upper urinary tract surgery were eligible for inclusion. Excluded were patients with a solitary kidney, suspected urothelial malignancy, or urinary tract infection. Following informed consent, all patients proceeded to the operating room. After induction of anesthesia, cystoscopy with ureteral catheterization was performed with urine collected via gravity drainage for 10 minutes. Urine samples with adequate volume were analyzed for chemistry concentrations. A difference greater than the 75 th percentile between matched pairs was considered significant. For urine pH, a difference of 0.5 was considered significant., Results: A total of 47 patients were screened for eligibility with only 13 (28%) electing to enroll in the study (26 renal units). All subjects underwent successful bilateral ureteral catheterization with no adverse events observed or later reported. The mean (± SD) urine volume captured from the right and left renal units was 5.0 ± 7.4 cm 3 and 6.6 ± 6.4 cm 3 , respectively. Urine was only captured from paired renal units in 8 participants (8/13; 62%). Of these 8 participants, 5 (5/8; 63%) had at least 1 unilateral metabolic defect., Conclusion: Unilateral renal unit urine sampling is safe and feasible. However, captured urine volumes are small and variable, but chemical analysis can still be performed. Unilateral defects in renal electrolyte handling are relatively common, but the clinical implications of these differences are still yet to be determined.
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Objectives: Ingestion of a concentrated low-volume phosphate solution produces copious diarrhea, which cleanses the colon, but it occasionally causes renal failure due to calcium phosphate precipitation in renal tubules. We hypothesized that a concentrated low-volume sulfate solution would be an equally effective cathartic, and that urine produced after sulfate would have less tendency to precipitate calcium salts than urine produced after phosphate., Methods: Hydrated subjects ingested 75 ml of phosphosoda or an equimolar dose of sulfate salts in a small volume of solution. Four liters of PEG (polyethylene glycol) lavage solution was the control. All solutions were administered in split doses, 10 h apart. Propensity of urine to precipitate at pH 6.4 (the pH of renal tubular fluid) was assessed by determining the minimal calcium concentration that caused precipitation., Results: Average diarrheal stool weight was 2,004 g after phosphate, 2,854 g after sulfate, and 3,021 g after PEG (P<0.001). Average calcium concentration (in mg/dl) required to induce urine precipitation at pH 6.4 was 43 after PEG, 10 after PO(4), and 187 after SO(4) (P=0.009)., Conclusions: (i) In equimolar doses, sulfate produced 42% more diarrheal stool weight than phosphate. (ii) Phosphate increased the propensity for calcium salt precipitation in urine at pH 6.4, whereas sulfate did not. (iii) These results suggest that a hypertonic low-volume sulfate solution would be an effective cathartic for colon cleansing and that sulfate-induced catharsis would be less likely than phosphate catharsis to produce calcium salt deposition in renal tubules.

The objective of this study was to evaluate the hypothesis that a high concentration of ionized calcium in the lumen of the medullary collecting duct causes an osmole-free water diuresis. The urine flow rate and osmolality were measured in normal human subjects, as well as in patients with a history of nephrolithiasis who excreted more than 5 mmol of calcium per 24 h. There was an inverse relationship between the concentration of calcium in the urine and the 24 h urine volume both in normal subjects and in patients with a history of nephrolithiasis. When the concentration of calcium in the urine was greater than 5 mmol/l, the urine volume was less than 1 litre per day in the majority of subjects. After 16 h of water deprivation, when the concentration of calcium in the urine was as high as 17 mmol/l (ionized calcium 7.4 mmol/l), urine osmolality was 1258 mOsm/kg of water and the urine flow rate was 0.30 ml/min. We conclude that, although a calcium receptor may be present in the lumen of the medullary collecting duct in human subjects, an extremely high concentration of urinary total and ionized calcium does not cause a clinically important defect in the renal concentrating process.

Urine produced by normal human kidneys is almost always supersaturated with respect to calcium oxalate (CaOx), the most common constituent of human kidney stones. Crystallization, with risk of renal damage and kidney stones, appears to be affected by molecules in urine that retard nucleation, growth, aggregation, and renal cell adherence of CaOx. The repertoire of such molecules is incompletely known. We have purified a 28-kDa protein from urine using salt precipitation, preparative isoelectric focusing, and sizing chromatography. Amino acid composition and NH2-terminal amino sequence analysis showed complete homology to calgranulin. Calgranulin was found to be a potent inhibitor of CaOx crystal growth (44% of control) and aggregation (50% of control) in the nanomolar range. Calgranulin cDNA was cloned from a human kidney expression library. Western analysis of human and rat kidney homogenates and mRNA temporal expression from two independent renal epithelial cell lines showed that calgranulin is produced in the kidney. Given its urinary abundance and potency, calgranulin may contribute importantly to the normal urinary inhibition of crystal growth and aggregation and therefore to the renal defense against clinical stone disease.

Kidney cells produce at least three proteins that slow the rate of calcium oxalate crystallization. Nephrocalcin (NC), one of the three, is an acidic glycoprotein that contains gamma-carboxyglutamic acid (GLA), and inhibits nucleation, aggregation and growth of calcium oxalate crystals. Nephrocalcin is abnormal in urine of stone-forming patients, in lacking GLA. It acts by absorbing to crystal surfaces. NC is produced by cultured renal proximal tubule cells, and by some lines of renal carcinoma cells, but its regulation is not yet characterized. Its sequence is not known, nor do we known the molecular basis for the abnormal character of NC is stone-forming patients. Compared to Tamm-Horsefall protein and uropontin, the two other inhibitors, NC is very potent, and is probably of major importance in protecting kidneys against supersaturations caused by normal water conservation.