Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients.

The natural history of post-extracorporeal shock wave lithotripsy residual stone fragments (clearance, growth and aggregation) is incompletely known, even though they are believed to constitute a risk in terms of new stone formation and persistent infection of the urinary tract. We addressed this issue and the hypothesis that alkaline citrate therapy improves residual stone fragment clearance in a 12-month followup study. There were 40 sterile calcium and 30 struvite stone patients with residual fragments after extracorporeal shock wave lithotripsy (diameter less than 5 mm.) consecutively enrolled and randomly assigned to a citrate therapy (6 to 8 gm. per day) or control (hygienic measures only) group. Infection stone patients also received adequate antibiotic therapy throughout the study. Among the patients in the untreated sterile group 21% and 32% were stone-free at 6 and 12 months, respectively. In the infection group these figures were 27% and 40%, respectively. Among the untreated sterile calcium stone patients in whom clearance was not achieved a high percentage experienced residual fragment growth or reaggregation. Citrate therapy significantly improved the stone clearance rate in the sterile (at 6 and 12 months 65% and 74% were stone-free, respectively) and infection (71% and 86%, respectively) stone patients, and prevented residual fragment growth or reaggregation in subjects in whom clearance was not achieved. The data show that growth and persistence are common in the natural history of residual stone fragments. Citrate ameliorated the outcome of these residual fragments by reducing the growth or agglomeration, and by increasing the clearance rate in calcium oxalate and in infection stone patients.

High urinary excretion of glycosaminoglycans: a possible marker of glomerular involvement in diabetes.

Many insulin-dependent diabetic patients with albuminuria in the "not at risk range" for diabetic nephropathy present high urinary excretion rates of glycosaminoglycans. A lysine provocative test in these subjects disclosed abnormal urinary excretion of albumin, unlike findings obtained in insulin-dependent diabetic patients with normal urinary excretion rates of glycosaminoglycans. These data support the hypothesis that high urinary excretion of glycosaminoglycans is a marker of glomerular involvement in diabetes mellitus.

Abnormal erythrocyte charge in diabetes mellitus. Link with microalbuminuria.

The anionic charge on the surface of the erythrocyte and the erythrocyte membrane content of sialic acid and acid glycosaminoglycans (GAGs) were evaluated in insulin-dependent diabetic patients who had albumin excretion rates less than 300 mg/24 h. In these subjects a statistically significant reduction of erythrocyte anionic charge (RBCCh) and GAGs content in erythrocyte ghosts was shown. In view of the demonstration of a negative correlation between RBCCh and albuminuria after a lysine provocative test, these observations support the hypothesis that the onset of microalbuminuria in human diabetes is sustained by an alteration of glomerular charge and consequently of glomerular charge selectivity.

Effects of imidazole-2-hydroxibenzoate on glycosaminoglycan and albumin urinary excretion in type 1 diabetic patients.

The effect of imidazole-2-hydroxibenzoate on urinary excretion rates of glycosaminoglycans and albumin in 22 insulin-dependent diabetics with albumin excretion rates under 300 mg/day was evaluated in a 165-day double blind crossover study. Unlike placebo, the drug reduced glycosaminoglycan and albumin excretion rates significantly after 40 and 60 days of treatment, and the effects were significantly intercorrelated. Moreover, a parallel reduction in urinary excretion of N-acetyl-beta-D-glucosaminidase was also observed. These pharmacological effects may have a positive impact on the subsequent natural history of diabetic nephropathy.

Urinary excretion of glycosaminoglycans in urological disease.

Altered urinary excretion of glycosaminoglycans (GAG) has been reported in patients with nephrolithiasis, with chronic glomerulonephritis, and incipient diabetic nephropathy, but evaluation of urinary GAG has not been reported in infections and proliferating diseases of the urinary tract. Urinary excretion of GAG was measured in 50 patients with idiopathic calcium nephrolithiasis (ICN) of whom 20 had associated urinary tract infection, in 20 subjects with recurrent infection of the urinary tract (UTI), and in 18 patients with bladder papillomatosis. Mean values were significantly lower in ICN, increased in papillomatosis, and in the normal range in UTI.

An inheritable anomaly of red-cell oxalate transport in "primary" calcium nephrolithiasis correctable with diuretics.

We measured the rate of oxalate flux across the red-cell membrane in the steady state in 114 patients with a history of calcium oxalate kidney stones and in 25 controls. Of the patients, 98 had recurrent, "idiopathic" kidney stones, 8 had primary hyperparathyroidism, 7 had renal or urinary tract malformations, and 1 had primary hyperoxaluria. Oxalate exchange was significantly higher in the 98 patients with idiopathic stone formation than in the controls (-1.10 +/- 0.95 [SD] X 10(-2) min-1 vs. -0.31 +/- 0.12 X 10(-2); P less than 0.001); it was above the upper limits of normal in 78 of these patients. All 8 patients with hyperparathyroidism and the patient with primary hyperoxaluria had values in the normal range; 2 of the patients with renal or urinary tract malformation had values at the upper normal limit. A study of five families indicated that the abnormality is an autosomal monogenic dominant trait with complete penetrance and variable expressivity. Oxalate-tolerance tests were carried out in five pairs of brothers. One brother in each pair had the abnormality in oxalate flux, and had a significantly higher percentage of oxalate excretion at two hours after oxalate loading (18.09 +/- 3.07 [SD] vs. 10.37 +/- 3.08 percent; t = 3.97; P less than 0.005) and four hours (14.87 +/- 2.91 vs. 9.89 +/- 2.93 percent; t = 2.70; P less than 0.05). Treatment with oral hydrochlorothiazide (50 mg per day) or amiloride (5 mg per day) or both restored normal or nearly normal red-cell oxalate exchange in all of 33 patients who initially had increased rates. We conclude that an inherited cellular defect in oxalate transport may be a factor in "primary" calcium oxalate stone formation and that this defect may be corrected with diuretics.

Urinary glycosaminoglycans, sialic acid and lysosomal enzymes increase in nonalbuminuric diabetic patients.

Urinary excretion of glycosaminoglycans (GAGS) and sialic acid (SA), as well as the activity of two renal enzymes related to glycoprotein metabolism, N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (GAL), and two others unrelated to glycosaminoglycans and glycoprotein metabolism, gamma-glutamyltranspeptidase (gamma-Gt) and angiotensin-I-converting enzyme (ACE), were evaluated in 40 insulin-dependent diabetic patients with normal range albuminuria, 21 patients with mesangial glomerulonephritis, and 30 control subjects. Diabetic and glomerulonephritic patients excreted a significantly higher amount of GAGS and SA, and showed greater NAG and GAL activities; gamma-Gt and ACE levels were within normal ranges. No correlation could be demonstrated between diabetes duration and GAGS, SA, NAG and GAL findings. Moreover, no correspondence between degree of metabolic control, as reflected by glycosylated hemoglobin (HbA1a-c) and GAGS, SA, NAG and GAL emerged.

A critical evaluation of the urinary inhibiting activity in idiopathic calcium oxalate nephrolithiasis.

In order to obtain new insights into the relevance of inhibitors in whole urine by focusing on their reciprocal interactions, a statistical approach was followed in 35 controls and 27 calcium oxalate (CaOx) recurrent idiopathic stone formers. The inhibiting activity of CaOx crystal growth and the most widely accepted inhibitors (glycosaminoglycans, citrate, magnesium, pyrophosphate), stone constituents (calcium, oxalate, phosphate, urate) and other normal urinary substances were evaluated. It was seen that the inhibitors played a very small role in total inhibiting activity. On the other hand, considering other normal urinary constituents, almost all the inhibiting power of urine on crystal growth could be explained.

Captopril in the treatment of hypertension in type I and type II diabetic patients.

Ten type I and 10 type II hypertensive diabetic patients were treated for 12 weeks with captopril (50 mg twice daily). Good control of blood pressure was achieved without any significant adverse effect on carbohydrate metabolism or renal haemodynamics and without evidence of glomerular or tubular damage.

Raised transmembrane oxalate flux in red blood cells in idiopathic calcium oxalate nephrolithiasis.

Red-blood-cell transmembrane oxalate flux was measured in a group of patients with idiopathic calcium oxalate nephrolithiasis and in normal controls. The mean transmembrane oxalate flux rate was significantly higher in stone-forming patients than in controls (0.93 +/- SD 0.31/min vs 0.29 +/- 0.11/min). 80% of stone-forming patients showed raised (greater than 2SD above the mean in controls) transmembrane oxalate flux. Anomalous cellular oxalate transport may be an important pathogenetic factor in calcium oxalate nephrolithiasis.

[Abnormalities in the erythrocyte membrane transport of oxalate in calcium oxalate lithogenesis]. / Anomalie du transport érythrocytaire de membrane de l'oxalate dans la lithogénèse oxalo-calcique.

The high incidence of a family history and the observation of abnormally high intestinal absorption and urinary excretion of oxalate suggest to consider idiopathic calcium oxalate nephrolithiasis as a metabolic disease characterized by a disorder in oxalate transport. To test this hypothesis, the flux of 14C Oxalate through the membrane of red blood cells was investigated in 24 calcium oxalate stone formers; 18 of the 24 "idiopathic" calcium oxalate stone formers showed an increased oxalate self exchange (75%). Our data seem to support the possibility that "idiopathic" calcium oxalate nephrolithiasis may be considered as a metabolic disease marked by a defect in transmembrane transport of oxalate.

[Role of Tamm-Horsfall mucoprotein in calcium oxalate lithogenesis]. / Rôle de la mucoprotéine de Tamm-Horsfall dans la lithogénèse oxalique-calcique.

Tamm-Horsfall (TH) mucoprotein has been suggested to play a lithogenetic role in calcium-oxalate nephrolithiasis. However it is still debated whether it promotes or inhibits crystal growth and aggregation. To make clear the role played by this mucoprotein, we have carried out the following experiments: 1) the urinary excretion of TH has been evaluated by radial immunodiffusion in 27 recurrent idiopathic CaOx stone formers and in 35 controls; 2) in a metastable solution of CaOx the effect of TH addition on crystal growth has been monitored; 3) in whole urine the effect of TH addition on crystal aggregation has been assayed by an aggregometer. Urinary excretion of TH is significantly lower in stone formers. TH does not seem to promote crystal growth, while it is effective on crystal aggregation. These data seem to suggest that the reduced excretion of TH in nephrolithiasis may be a lithogenic risk factor.