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Paul Jungers

Publications and source records attributed to Paul Jungers.

At least 19 recordsLinked to original sources
PubMed2006

Influence of body size on urinary stone composition in men and women.

A larger body size has been shown to be associated with increased excretion of urinary lithogenic solutes, and an increased risk of nephrolithiasis has been reported in overweight patients. However, the type of stones produced in these subjects has not been ascertained. Based on a large series of calculi, we examined the relationship between body size and the composition of stones, in order to assess which type of stone is predominantly favoured by overweight. Among 18,845 consecutive calculi referred to our laboratory, 2,100 came from adults with recorded body height and weight. Excluding calculi from patients with diabetes mellitus, as well as struvite and cystine stones, the study material consisted of 1,931 calcium or uric acid calculi. All calculi were analysed by infrared spectroscopy and categorized according to their main component. Body mass index (BMI) values were stratified as normal BMI (< 25 kg/m2), overweight (BMI 25-29.9) or obese (BMI > or = 30). Overall, 27.1% of male and 19.6% of female stone formers were overweight, and 8.4 and 13.5% were obese, respectively. In males, the proportion of calcium stones was lower in overweight and obese groups than in normal BMI group, whereas the proportion of uric acid stones gradually increased with BMI, from 7.1% in normal BMI to 28.7% in obese subjects (P<0.0001). The same was true in females, with a proportion of uric acid stones rising from 6.1% in normal BMI to 17.1% in obese patients (P=0.003). In addition, the proportion of uric acid stones markedly rose with age in both genders (P<0.0001). The average BMI value was significantly higher in uric acid stone formers aged < 60 years than in all other groups, whereas it did not differ from other groups in those aged > or = 60 years. Stepwise regression analysis identified BMI and age as significant, independent covariates associated with the risk of uric acid stones. Our data provide evidence that overweight is associated with a high proportion of uric acid stones in patients less than 60 years of age, whereas beyond this limit, advancing age is the main risk factor.

Adult↗
PubMed2006

[Continued late referral of patients with chronic kidney disease. Causes, consequences, and approaches to improvement].

OBJECTIVES: Efforts in recent years have aimed at increasing physicians' awareness of the frequent and harmful consequences of late referral to nephrologists of patients with chronic kidney disease (CKD), shown in repeated concordant studies. We sought to determine whether these efforts have led to improved predialysis care of these patients. METHODS: This study included all 1391 consecutive patients who began maintenance dialysis at Necker Hospital between January 1989 and December 2000. We examined baseline data and outcomes and determined for four three-year periods the percentage of patients who received early specialized care (at least 6 months before onset of dialysis). RESULTS: Late referral (<6 months before dialysis) did not change significantly over the four periods, remaining around 30%, even during the most recent period (1998-2000). Clinical condition and laboratory indicators of patients referred early but not those referred late improved in the latest period, compared with the initial period (1989-1991). Overall, prevalence of major cardiovascular events (myocardial or cerebral infarction, peripheral arteriopathy, or heart failure) was more than twice as high in patients who received nephrologic care for less than 6 months and nearly twice as high even in those followed 6-35 months than in patients followed for at least 36 months before beginning dialysis. Subsequent mortality after maintenance dialysis was also significantly higher in patients with late referral than in those followed at least 3 years before dialysis. Multivariate Cox proportional model analysis identified graded duration of predialysis nephrologic care as a significant independent factor predictive of risk of mortality while on dialysis. CONCLUSION: Late referral of CKD patients for specialist care remains frequent, around 30%, although it is most often unjustified. Late referral deprives the patient of early implementation of a reno- and cardioprotective therapeutic strategy that reduces cardiovascular comorbidity and mortality. Better coordinated cooperation between family doctors and nephrologists, through the implementation of regional healthcare networks, now appears as the most effective way to improve the care of CKD patients.

Acute Kidney Injury↗
PubMed2005

Advanced oxidation protein products as risk factors for atherosclerotic cardiovascular events in nondiabetic predialysis patients.

BACKGROUND: Inflammation and oxidative stress are established risk factors for atherosclerosis, but whether they contribute to the accelerated atherogenesis associated with chronic kidney disease (CKD) remains to be assessed at the predialysis stage. METHODS: We prospectively examined the relationship between plasma levels of C-reactive protein (CRP), fibrinogen, and advanced oxidation protein products (AOPPs), as selected markers of inflammation and oxidative stress, and incident first occlusive atherosclerotic cardiovascular (CV) events (ASCVEs) in a single-center cohort of 80 uremic predialysis patients without diabetes with a creatinine clearance ranging from 20 to 40 mL/min/1.73 m2 . RESULTS: During follow-up (median, 7 years), 21 patients developed coronary, cerebral, or peripheral artery occlusive accidents, an incidence of 44/1,000 patient-years. Except for older age, their conventional risk factors did not differ compared with the 59 patients who remained free of such accidents. Conversely, plasma levels of CRP (4.3 +/- 2.7 versus 2.3 +/- 2 mg/L; P = 0.005), fibrinogen (5.6 +/- 1.4 versus 4.4 +/- 1.2 mg/L; P = 0.0009), and AOPPs (58 +/- 20 versus 42 +/- 14 micromol/L; P = 0.0002) were significantly greater at baseline, although serum creatinine levels did not differ between the 2 groups. By multivariate Cox regression analysis, age and CRP, fibrinogen, and AOPP levels were significant independent predictors of ASCVEs. Risk factor-adjusted hazard ratios were as follows: age, 1.13 (95% confidence interval, 1.04 to 1.22; P = 0.002); CRP level, 1.37 (95% confidence interval, 1.05 to 1.79; P = 0.02); fibrinogen level, 2.23 (95% confidence interval, 1.20 to 4.13; P = 0.011); and AOPP level, 1.68 (95% confidence interval, 1.12 to 2.51; P = 0.011). CONCLUSION: CRP, fibrinogen, and AOPP levels independently predict ASCVEs in patients with CKD in the predialysis phase and might directly contribute to the uremia-associated accelerated atherogenesis.

Arteriosclerosis↗
PubMed2005

Serial crystalluria determination and the risk of recurrence in calcium stone formers.

BACKGROUND: Urinary crystal precipitation is the necessary initial step in kidney stone formation. However, clinical relevance of crystalluria in the evaluation of stone formers is disputed. METHODS: We serially determined crystalluria in first-voided morning urine samples, together with full 24-hour urine biochemistry, in 181 patients with idiopathic calcium nephrolithiasis who had formed at least one calcium-oxalate stone and were followed for at least 3 years under our care. All stone events which occurred prior to referral, then after entry in the study were recorded. RESULTS: As compared with 109 patients who had no evidence of stone recurrence during follow-up, the 72 patients who experienced >/= one recurrent stone event had a lower daily urine volume (1.74 +/- 0.06 vs. 2.26 +/- 0.05 L/day (mean +/- SEM) (P < 0.0001), higher urine calcium and oxalate concentrations, and daily calcium excretion, and they had more frequent crystalluria (68% vs. 23% of urine samples) (P < 0.0001). By multivariate Cox regression analysis, the hazard ratio for stone recurrence was 0.32 (95% CI 0.16-0.62) for 1 L increase in daily urine volume, 1.12 (1.09-1.24) for 1 mmol/L increase in urine calcium concentration, 1.24 (1.02-1.50) for 0.1 mmol/L increase in urine oxalate concentration and 27.8 (10.2-75.6) for crystalluria index. CONCLUSION: These data provide evidence that crystalluria, when repeatedly found in early morning urine samples, is highly predictive of the risk of stone recurrence in calcium stone formers. Serial search for crystalluria, a simple and cheap method, may be proposed as a useful tool for the monitoring of calcium stone formers, in addition to urine biochemistry.

Adolescent↗
PubMed2005

Prediction model of coronary heart disease in patients with chronic kidney disease: role of plasma fibrinogen as a new prognostic variable.

BACKGROUND: The Framingham-Anderson (FA) risk equation can predict coronary heart disease (CHD) risk in the general population. However, this formula's validity in predicting CHD risk in chronic kidney disease (CKD) patients is not extensively evaluated. METHODS: In a group of 96 patients with CKD stage 2 to 4, free of CHD at the time of the start of follow-up, and prospectively followed for 4 to 12 years (7.4 +/- 2.2 years, mean +/- SD), we calculated the FA index. RESULTS: During the follow-up period, twenty-one patients experienced fatal and non-fatal myocardial infarction (CHDobs+), and 75 remain free of CHD (CHDobs-). The median FA index was 7.1% for CHDobs - patients and 10.3% for CHDobs+ patients. The specificity of the model was acceptable (89%), but the sensitivity was low (24%). Sensitivity analysis by adding fibrinogen led to an improvement in the CHD risk index and the sensitivity of the model (48%) as well. However, despite the addition of fibrinogen to the FA risk factors, full CHD risk in CKD patients remains underestimated. CONCLUSIONS: Our results show that the FA index is a weak predictor of CHD in CKD stage 2 to 4 patients, and emphasized the role of inflammation in predicting the CHD risk.

Aged↗
PubMed2004

Changes in stone composition according to age and gender of patients: a multivariate epidemiological approach.

Urinary stone incidence and composition have changed markedly over the past half-century in industrialized countries, in parallel with profound changes in living standards and dietary habits, with a dramatic increase in the incidence of calcium oxalate stones. However, studies evaluating the influence of age and gender on the distribution of the various types of urinary calculi are scarce. We report the results of a study based on 27,980 calculi (from 19,442 males and 8,538 females) analyzed by infrared spectroscopy between 1976 and 2001. The relationships between age and sex and stone composition were investigated using a multivariate approach, based on correspondence factor analysis (CFA). We found a male predominance for calcium oxalate and uric acid, a female preponderance for calcium phosphate and struvite stones, and an increasing prevalence of uric acid stones with age in both genders. CFA was able to reconstruct in blind the age curve from stone composition. The first two axes of the multidimensional classification, which correspond to age, included 86.9% of the total variance, indicating that age was the main factor involved in stone type. Superimposition of age classes and stone components showed a strong relationship between age and whewellite, weddellite, brushite, carbapatite, octacalcium phosphate and uric acid, while other substances (whitlockite, amorphous carbonated calcium phosphate, struvite, proteins, mucopolysaccharides, triglycerides or ammonium urate) appeared weakly related to age. In addition, CFA suggests the role of common lithogenic factors between weddellite, carbapatite and brushite, which clustered in the same area, whereas the various crystalline forms of phosphate stones segregated into two different clusters, suggesting distinct pathogenic factors. In conclusion, this study provides a picture of the present epidemiology of urinary stones in France. CFA helped to confirm: (1) an etiopathogenic distinction between weddellite and whewellite, (2) etiopathogenic associations between chemical compounds, which were only suspected on a clinical basis, and (3) suggested yet unrecognized associations, especially with respect to the heterogeneous group of phosphate stones.

Adolescent↗
PubMed2004

Early prediction of IgA nephropathy progression: proteinuria and AOPP are strong prognostic markers.

BACKGROUND: Inflammation and oxidative stress have been incriminated in the pathogenesis of IgA nephropathy (IgAN). The aim of the present study was to assess whether markers reflecting these pathophysiologic processes, namely C-reactive protein (CRP) and advanced oxidation protein products (AOPP), would allow-in conjunction with clinical and histopathologic parameters-to predict disease progression. METHODS: Between 1994 and 1997, 120 adult patients with biopsy-proven IgAN were included in a prospective cohort study, and followed until the end of 2002 or start of dialysis. In every patient, we determined plasma levels of CRP and AOPP. These parameters were included, together with clinical data, in a multivariate Cox proportional hazard regression analysis, with halving of baseline creatinine clearance as the primary renal end point. RESULTS: A total of 51 patients reached the renal end point, including 30 who had to start dialysis. With multivariate analysis, the most potent independent risk factors of poor renal outcome were proteinuria > or =1 g/day [proportional hazard risk (HR) = 23.7, P= 0.0001], hypertension (HR = 8.13, P= 0.008), and AOPP plasma level (HR = 1.09 per 10 micromol/L, P= 0.042), whereas angiotensin II inhibitors were protective (HR = 0.19, P= 0.001). CONCLUSION: Our data support the role of oxidative stress in the pathogenesis of IgAN and suggest that patients with proteinuria > or =1 g/day should be eligible for early implemented antioxidant and/or anti-inflammatory therapeutic strategies, with AOPP plasma level as a surrogate marker to evaluate their effects.

Adult↗
PubMed2004

Clinical value of crystalluria and quantitative morphoconstitutional analysis of urinary calculi.

Morphoconstitutional analysis of urinary calculi, i.e. morphologic examination combined with Fourier transform infrared spectroscopy (FTIR), is of decisive interest for the diagnosis of rare but severe inherited or acquired stone diseases such as cystine, 2,8-dihydroxyadenine, xanthine, struvite, ammonium urate or drug-containing calculi as well as primary hyperoxalurias. In the absence of early diagnosis and proper management, these diseases may lead to progressive loss of renal function. Among common forms of calcium oxalate (CaOx) stones, predominant CaOx monohydrate (whewellite) is mainly associated with hyperoxaluric conditions whereas predominant CaOx dihydrate (weddellite) is mainly associated with hypercalciuria, and this distinction is of interest to orient metabolic evaluation and preventive measures. Crystalluria examination, also based on morphology and FTIR, is a valuable diagnostic method when no stone is available for analysis. Presence of specific crystals (cystine, 2,8-dihydroxyadenine, struvite, ammonium urate) is diagnostic by itself. In all types of nephrolithiasis, serial crystalluria determination appears as a simple, cheap and reliable method to evaluate the risk of stone formation and assess the effectiveness of preventive measures. Determination of urinary crystal volume was in our experience a useful tool in the management of patients with cystinuria or primary hyperoxaluria in the post-transplantation period. In conclusion, both accurate morphologic and FTIR analysis of stones and serial crystalluria determination should be more largely used, in view of their value in the diagnosis and management of renal stone formers.

Crystallization↗
PubMed2004

Drug-induced renal calculi: epidemiology, prevention and management.

Drug-induced calculi represent 1-2% of all renal calculi. The drugs reported to produce calculi formation may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favours crystallisation in the urine. Among poorly soluble molecules, triamterene was the leading cause of drug-containing urinary calculi in the 1970s, and it is still currently responsible for a significant number of calculi. In the last decade, drugs used for the treatment of HIV-infected patients, namely indinavir and sulfadiazine, have become the most frequent cause of drug-containing urinary calculi. Besides these drugs, about twenty other molecules may induce nephrolithiasis in patients receiving long-term treatment or high doses. Calculi analysis by physical methods, including infrared spectroscopy or x-ray diffraction, is needed to demonstrate the presence of the drug or its metabolites within the calculi. The second group includes drugs that provoke urinary calculi as a consequence of their metabolic effects. Here, diagnosis relies on careful clinical inquiry because physical methods are ineffective to differentiate between urinary calculi induced by the metabolic effects of a drug and common metabolic calculi. The incidence of such calculi, especially those resulting from calcium/vitamin D supplementation, is probably underestimated. Although drug-induced urinary calculi most often complicate high-dose, long-duration drug treatments, there also exist specific patient risk factors in relation to urine pH, urine output and other parameters, which provide a basis for preventive or curative treatment of calculi. Better awareness of the possible occurrence of lithogenic complications, preventive measures based on drug solubility characteristics and close surveillance of patients on long-term treatment with drugs with lithogenic potential, especially those with a history of urolithiasis, should reduce the incidence of drug-induced nephrolithiasis.

Drug-Related Side Effects and Adverse Reactions↗
PubMed2004

ESRD caused by nephrolithiasis: prevalence, mechanisms, and prevention.

BACKGROUND: The contribution of nephrolithiasis-related end-stage renal disease (ESRD) to patients requiring renal replacement therapy has never been specifically evaluated. METHODS: Of the entire cohort of 1,391 consecutive patients who started maintenance dialysis therapy at our nephrology department between January 1989 and December 2000, a total of 45 patients (21 men) had renal stone disease as the cause of ESRD and constitute the study material. Type and cause of renal stone disease was determined in the 45 patients, as well as the change in prevalence of nephrolithiasis-related ESRD with time during this 12-year period. RESULTS: The overall proportion of nephrolithiasis-related ESRD was 3.2%. Infection (struvite) stones accounted for 42.2%; calcium stones, 26.7%; uric acid nephrolithiasis, 17.8%; and hereditary diseases (including primary hyperoxaluria type 1 and cystinuria), 13.3% of cases. Women were predominant among patients with infection and calcium stones, whereas men were predominant among patients with uric acid or hereditary stone disease. The proportion of patients with nephrolithiasis-related ESRD decreased from 4.7% in the triennial period 1989 to 1991 to 2.2% in the most recent period, 1998 to 2000 ( P = 0.07). This tendency to a decreasing prevalence mainly was caused by a rarefaction of infection and calcium stones with time, whereas frequencies of uric acid and hereditary stone disease remained essentially unchanged. CONCLUSION: Severe forms of nephrolithiasis remain an underestimated cause of potentially avoidable ESRD and need for renal replacement therapy. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and proper therapy for conditions that may lead to ESRD through recurrent stone formation and/or parenchymal crystal infiltration.

Adult↗
PubMed2004

[Lithogenesis].

Explore the source record for details and available documents.

Crystallization↗
PubMed2003

Cystine crystal volume determination: a useful tool in the management of cystinuric patients.

We prospectively determined cystine crystal volume (Vcys) in urine specimens from all consecutive patients with cystine urolithiasis followed at our institution over the past decade, in order to assess its predictive value as to the risk of recurrent cystine stone formation. A total of 57 patients (29 males, 28 females) with homozygous cystinuria entered in the study between January 1990 and December 2000, including 15 children aged less than 15 years and 42 patients aged 15 years or more. The clinical and radiological course was followed until December 2001, for a total of 243 patient-years of follow-up. From study entry until the end of follow-up, we serially examined first voided morning urine specimens in all patients, with determination of the number of cystine crystals per mm3, and the average size of crystals, thus allowing us to calculate Vcys using a simple formula based on crystal geometry. Recurrence was diagnosed on the basis of serial radiographic examinations using X-rays and echography. Overall, cystine crystals were present in 179 (39%) of the 460 examined urine specimens. Cystine crystalluria was significantly more frequent among the 27 patients who developed new cystine stones (SF) than in the other 30 who remained stone-free (63.3 vs 25.5% of samples, P<0.001). The presence of crystals in > or =50% of serially examined urine samples was more frequently found in patients with recurrent stone formation than in non-recurrent patients (24/27 vs 2/30, P<0.001). The average Vcys value was significantly higher in recurrent SF than in stone-free patients (8,173 +/- 1,544 vs 233 +/- 150 micro3/mm3, P<0.001) and there was no overlap in the individual values of recurrent vs stone-free patients. A Vcys value > or =3,000 micro3/mm3 was observed at least once prior to each of the 63 stone recurrences observed in 27 patients (2.3 per patient on the average). In addition, Vcys reflected the efficacy of treatment, with Vcys mean values of 12,097 +/- 3,214 micro3/mm3 at baseline, falling to 2,648 +/- 658 micro3/mm3 on basic therapy (hyperdiuresis plus alkalinization) alone, 1,141 +/- 522 micro3/mm3 on tiopronin therapy (median dose 1,000 mg/day) and 791 +/- 390 micro3/mm3 on D-penicillamine therapy (median dose 900 mg/day) whereas captopril had no effect (5,114 +/- 2,128 micro3/mm3). Based on the results of the present study, cystine crystalluria appears to accurately reflect active stone formation in cystinuric patients. Determination of total Vcys provides a simple, cheap and accurate means of predicting the risk of cystine stone recurrence with a Vcys value > or =3000 micro3/mm3 as the threshold risk value. We propose that serial Vcys determination be performed simultaneously with the measurement of urine pH and specific gravity to optimally monitor the medical treatment of cystine patients.

Adolescent↗
PubMed2003

[Frequency of anaemia and indications for treatment with epoetin in chronic renal failure at the pre-dialysis stage].

OBJECTIVES: To determine the degree of anaemia corresponding to the decreasing levels of renal function in patients with chronic renal failure (CRF) and not yet on dialysis, and to assess the indications for treatment with recombinant erythropoeitin (epoetin). METHODS: We studied the relationship between haemoglobin (Hb) concentration and creatinine clearance (Ccr) in 403 consecutive patients with CRF regularly monitored in nephrology consultations between January 1 and June 30, 1999, and who received appropriate iron and vitamin supplementation. These patients were then followed-up until June 30, 2000 or until maintenance dialysis was initiated. RESULTS: There was a significant and close correlation between the degree of anaemia and renal dysfunction. An Hb value<11 g/dl (corresponding to the present threshold for the indication of epoetin) was observed in 62% of patients with creatinine levels>400 micromol/l and in 58% when Ccr was<20 ml/mn/1.73 m2. Whatever the level of CRF, the degree of anaemia was higher in the women than in the men. Among the 123 patients who had to start maintenance dialysis during the observation period, 85 (69%) were treated with epoetin before dialysis was started. CONCLUSION: In patients with CRF, clinically symptomatic anaemia is more frequent than imagined, and early treatment is required. Regular monitoring of Hb and iron levels is mandatory in order to allow patients to benefit from timely initiation of epoetin and thus prevent the development of disabling asthenia and other deleterious consequences of anaemia.

Adult↗
PubMed2003

Octogenarians reaching end-stage renal disease: cohort study of decision-making and clinical outcomes.

The fate of octogenarians reaching end-stage renal disease (ESRD) is poorly defined, and implicit dialysis rationing may be practiced in this age group. The main objectives of this study were to analyze the characteristics of pre-ESRD octogenarians offered dialysis or not and to identify factors influencing mortality while on dialysis, to improve prognosis assessment and decision-making. In this single-center cohort, 146 consecutive pre-ESRD octogenarians were referred to a nephrology unit over a 12-yr period (1989 to 2000). Main outcome measures were baseline characteristics of patients offered dialysis and conservative therapy and overall and 1-yr survival according to effective treatment. A therapeutic decision was made for 144 patients. Octogenarians who were not proposed dialysis (n = 37) differed from those who were proposed dialysis (n = 107) mainly in terms of social isolation (43.3% versus 14.7%; P = 0.03), late nephrologic referral (51.4% versus 28.9%; P = 0.01), Karnofsky score (55 +/- 18 versus 63 +/- 20; P = 0.03), and diabetic status (22.2% versus 6.5%, P = 0.008). Six patients refused the dialysis proposal. During the 12-yr observation period, 99 patients died (68.7%). Median survival was 28.9 mo (95% CI, 24 to 38) in patients undergoing dialysis, compared with 8.9 mo (95% CI, 4 to 10) in patients treated conservatively (P < 0.0001). In multivariable piecewise Cox analysis, independent predictors of death within 1 yr on dialysis were poor nutritional status, late referral, and functional dependence. Included in a survivor function, these covariates predict groups with low and high 1-yr mortality risk. Beyond 1 yr on dialysis, the only independent predictor of death was the presence of peripheral vascular disease. It is concluded that beside a patient's individual refusal, late referral, social isolation, low functional capacity, and diabetes may have oriented medical decision toward withholding dialysis in a significant proportion of pre-ESRD octogenarians. Although most patients on dialysis experienced a substantial prolongation of life, identification of mortality predictors in this age group should improve the process of decision-making regarding the expected benefit of renal replacement therapy.

Aged↗
PubMed2003

[Urinary stones and urinary tract abnormalities. Is the stone composition independent of the anatomical abnormality?].

INTRODUCTION: More than ten per cent of stones are associated with a urinary tract abnormality. To verify whether the malformation influences stone composition, we studied the composition of stones observed in fifteen urological abnormalities. MATERIAL AND METHOD: This study is based on 1,461 stones associated with a clearly defined malformation analysed by infrared spectroscopy plus 402 bladder stones in men with benign prostatic hyperplasia. RESULTS: In this series of 1,863 abnormalities, 732 (39.3%) involved the kidney, 561 (30.1%) involved the ureter and 570 (30.6%) involved the lower tract. Whewellite stones were predominant in all renal abnormalities with the exception of cysts, which were mainly associated with uric acid. The main differences concerned the second constituent: weddellite in horseshoe kidneys, carbapatite in Cacchi-Ricci disease and caliceal abnormalities. Struvite was uncommon (<10%). Whewellite was the main component in ureteric abnormalities except for megaureter and reflux in which carbapatite was predominant. Struvite was present in 10% to 30% of stones. Vesicourethral abnormalities were accompanied by calcium and magnesium phosphate stones (90% of cases), and struvite was present in 58% to 90% of cases. The exception to this general rule was bladder stones associated with benign prostatic hyperplasia, in which the main component was uric acid. CONCLUSION: Significant differences in stone composition were observed as a function of anatomical abnormalities reflecting the fact that some abnormalities add infectious or metabolic risk factors to anatomical factors.

Female↗