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PubMed1982

Incidence of radiographically evident bone disease, nephrocalcinosis, and nephrolithiasis in various types of renal tubular acidosis.

The syndrome of renal tubular acidosis has been categorized into three physiologic types that have different clinical findings and prognostic and therapeutic implications. We reviewed radiographs of the skeleton and kidneys in 92 patients (56 children and 36 adults) with renal tubular acidosis in order to determine whether the radiologic findings could be related to the type of syndrome. Forty-four patients had Type 1 renal tubular acidosis, 18 had Type 2, and 30 had Type 4. Evidence of skeletal abnormalities was uncommon (17 per cent) and was confined to patients who had the Type 2 disorder or azotemia. The children with Type 2 and skeletal abnormalities had rickets; the adults had osteopenia without pseudofractures. Nephrocalcinosis was evident in approximately one fourth of the group (29 per cent) and was restricted to patients with the Type 1 syndrome. In patients with Type 4, osteopenia was evident in 12 per cent, all of whom were azotemic. Our observations indicate that the radiographic manifestations of renal tubular acidosis are influenced by the physiologic type of renal tubular acidosis.

Acidosis, Renal Tubular↗
PubMed1986

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.

Adolescent↗
PubMed2002

Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter.

BACKGROUND: Epidemiologic studies suggest that genetic factors confer a predisposition to the formation of renal calcium stones or bone demineralization. Low serum phosphate concentrations due to a decrease in renal phosphate reabsorption have been reported in some patients with these conditions, suggesting that genetic factors leading to a decrease in renal phosphate reabsorption may contribute to them. We hypothesized that mutations in the gene coding for the main renal sodium-phosphate cotransporter (NPT2a) may be present in patients with these disorders. METHODS: We studied 20 patients with urolithiasis or bone demineralization and persistent idiopathic hypophosphatemia associated with a decrease in maximal renal phosphate reabsorption. The coding region of the gene for NPT2a was sequenced in all patients. The functional consequences of the mutations identified were analyzed by expressing the mutated RNA in Xenopus laevis oocytes. RESULTS: Two patients, one with recurrent urolithiasis and one with bone demineralization, were heterozygous for two distinct mutations. One mutation resulted in the substitution of phenylalanine for alanine at position 48, and the other in a substitution of methionine for valine at position 147. Phosphate-induced current and sodium-dependent phosphate uptake were impaired in oocytes expressing the mutant NPT2a. Coinjection of oocytes with wild-type and mutant RNA indicated that the mutant protein had altered function. CONCLUSIONS: Heterozygous mutations in the NPT2a gene may be responsible for hypophosphatemia and urinary phosphate loss in persons with urolithiasis or bone demineralization.

Adult↗
PubMed2004

Childhood idiopathic hypercalciuria--clinical significance of renal calyceal microlithiasis and risk of calcium nephrolithiasis.

OBJECTIVE: To evaluate the clinical significance of renal calyceal microlithiasis (RCM) in children with idiopathic hypercalciuria (IHC). MATERIAL AND METHODS: RCM is a renal echographic finding defined as the presence of hyperechogenic spots < 3 mm in diameter in the renal calyces. These spots have been associated with the presence of nephrourological symptoms in children and are considered to represent a stage prior to urolithiasis. We reviewed the medical records of 103 children (63 girls, 40 boys; age range 1-14 years; mean age 6.57 years) referred for various complaints who had IHC. Renal echography was routinely performed. At diagnosis, 52 children had RCM, 35 showed normal echography, 14 had calculi and two presented nephrocalcinosis. A long-term follow-up study was carried out to compare the clinical manifestations, analytic data and renal echographic findings of patients with RCM and those with normal echography. RESULTS: The clinical manifestations and the results of biochemical studies did not differ significantly between the two groups. Renal sonographic findings during the follow-up period revealed that, of patients with initial RCM, 35 showed normalized sonographic findings, two developed calculi and 36 developed recurrent RCM. Of the children with normal initial echography, 17 developed RCM and three developed calculi. The risk of developing lithiasis was less in children with RCM than in those with normal initial renal echography (0.04 vs 0.09), the relative risk being 0.45 (95% CI 0.08-2.55). The clinical and analytic differences between the group of 14 children with initial lithiasis and the other two groups previously described were also analyzed and no significant differences were found. An ongoing echographic study of these patients showed that the echograph was normalized in 10 children at some point or other, while seven developed RCM (four unilateral, three bilateral). In 13 cases the lithiasis reappeared, and the relative risk of recurrent lithiasis compared with those who initially showed no lithiasis was 16.16 (CI 95% 6.81-38.31). CONCLUSION: Our results indicate that up to 85% of children with IHC presented RCM in follow-up sonographies. This echographic finding, which may appear and disappear at different points during follow-up, does not seem to indicate an increased risk of lithiasis.

Adolescent↗
PubMed2005

Nephrolithiasis as primary symptom in sarcoidosis.

A 30-year-old black woman presented with a 1-year history of repeated episodes of worsening weight loss and fatigue. Physical examination showed no skin lesions and a chest roentgenogram was normal. Workup showed no obvious cause of recurrent renal stones. Finally, the detection of lymphadenopathy led to the diagnosis of extrapulmonary sarcoidosis. Up to 4% of all cases of sarcoidosis may present with urolithiasis only. Renal stones may be more common in severe cases of sarcoidosis, which affect blacks most frequently. Although not generally recommended for diagnostic purposes in sarcoidosis, in this case determination of the angiotensin-converting enzyme level was helpful in making the correct diagnosis. It is important that physicians are aware of the possibility that sarcoidosis may present as urolithiasis, even in the presence of a negative chest roentgenogram.

Adult↗
PubMed1995

A practical approach to nephrolithiasis.

Detailed metabolic evaluation and prophylaxis for all patients presenting with a first renal stone seems inappropriate. The crucial clinical problem lies in predicting which patients are likely to have a recurrence. Stone composition is an important guide for the physician's decisions concerning investigation and a rational choice of treatment.

Calcium↗
PubMed1976

Kidney function during hydropenia nad water diuresis in patients with idiopathic recurring nephrolithiasis.

The kidney function of 41 patients with idiopathic recurring kidney stones was investigated by inulin- and PAH-clearances and by measuring the excretion of electrolytes during hydropenia and water diuresis. All patients had normal inulin- and PAH-clearances and normal concentrating capacity as indicated by free water reabsorption (Tc H2O). Seven patients, all of whom had previously been found to have low excretion of magnesium in urine, were unable to dilute their urine. During water diuresis these patients also had lower osmolar clearance and lower excretion of sodium than the other patients. A defective dilution capacity may be of pathogenetic significance for stone formation; the causes of the defect, however, are not clear.

Adult↗
PubMed1999

Meta-analysis of randomized trials for medical prevention of calcium oxalate nephrolithiasis.

OBJECTIVES: To determine the efficacy of commonly used medications in comparison with placebo or no treatment for the prevention of renal stone recurrence (metaphylaxis) as documented in the literature. METHODS: A MEDLINE search identified 14 randomized, controlled trials comprising 20 treatment arms and 6 different drug therapies for the prevention of stone recurrence. The active treatment arms from each of the trials were combined, and the results were compared with those of the control or no treatment arms overall and for each category of drug therapy (thiazide diuretics, allopurinol, phosphate, magnesium, and alkali citrate). A meta-analysis was performed of the combined treatment and control arms for all trials from which sufficient data were provided, both for overall medical therapy and for thiazide treatment. RESULTS: A statistically significant benefit of drug therapy for stone metaphylaxis was identified (P = 0.04), largely because of the benefit of thiazides compared with placebo or no treatment (P = 0.02). Allopurinol conferred no overall benefit, although the only trial evaluating therapy in hyperuricosuric patients showed a statistically significant benefit. CONCLUSION: Medical therapy for calcium stone disease reduces the incidence of recurrence. Although only thiazide diuretics among the drug therapies were shown to significantly reduce stone recurrence, variability in study design and study population precluded adequate analysis of other drug therapies such as alkali citrate. Standardization of study design and reporting should improve the evaluation of the efficacy of new drug treatments.

Allopurinol↗
PubMed2004

Progression of nephrolithiasis: long-term outcomes with observation of asymptomatic calculi.

BACKGROUND AND PURPOSE: Observation is often recommended for patients presenting with asymptomatic renal calculi. This study evaluated the natural history of asymptomatic calculi and the risk of progression of disease. PATIENTS AND METHODS: We conducted a retrospective evaluation of 300 male patients average age 62.8 years who were followed for a mean of 3.26 years for asymptomatic renal calculi in an outpatient urology clinic. At presentation, the mean cumulative stone diameter was 10.8 mm; 56% were lower-pole stones, and 48% of the patients had multiple calculi. Patients underwent annual radiographic imaging and clinic visits with standardized questions regarding the development of symptoms or complications from calculi. Progression of disease was defined as the need for surgical intervention, the development of pain, or stone growth on serial imaging. RESULTS: Overall, 77% of patients experienced disease progression, with 26% requiring surgical intervention. Stone size was positively associated with progression: those with an isolated stone >/=4 mm on presentation were 26% more likely to fail observation than patients with smaller solitary calculi (P = 0.012). Stone growth was less common in those with upper-pole and middle-pole stones (47% v 61%) for lower-pole stones; P = 0.002). Urine uric acid concentration correlated positively with the rate of stone growth (P = 0.05). Likewise, serum uric acid concentration predicted stone growth (odds ratio = 3.6). CONCLUSIONS: Stratification of risk of progression according to presenting stone size, location, and composition may facilitate discussions with the patient regarding the alternatives of observation versus intervention. Specifically, small non-uric acid calculi in the upper pole may be most amenable to observation.

Adult↗