Low Urine pH Research Articles

An association between kidney stone composition and urinary metabolic disturbances in children

ObjectiveTo determine kidney stone composition in children and to correlate stone fractions with urinary pH and metabolic urinary risk factors. Patients and methodsWe studied 135 pediatric patients with upper urinary tract lithiasis in whom excreted or extracted stones were available for analyses. Composition of stones was analyzed. A 24-hour urine assessment included volume, pH and daily excretions of calcium, oxalate, uric acid, cystine, creatinine, phosphate, magnesium and citrate. ResultsCalcium oxalate was the major component of 73% stones, followed by struvite (13%) and calcium phosphate (9%). Uric acid was present in almost half of stones, but in rudimentary amounts. The calcium oxalate content in calculi showed a strong relationship with calciuria, and moderate association with oxaluria, magnesuria and acidification of urine. The percent content of struvite presented reverse and lower correlations with regard to the above parameters. Calcium phosphate stone proportion had low associations with urinary risk factors. ConclusionsCalciuria, oxaluria, magnesuria and low urine pH exerted the biggest influence on calcium oxalate content in pediatric renal stones. Relationships of urinary risk factors with calculi calcium phosphate content were of unclear significance. Urinary citrate excretion did not significantly correlate with kidney stone composition in children.

Increased intrarenal expression of sodium-dicarboxylate cotransporter-1 in nephrolithiasis patients with acidic urine pH.

Background: Low urinary excretion of citrate is a major risk in Thai kidney stone patients. Reabsorption of citrate at renal proximal tubules requires sodium-dicarboxylate cotransporter-1 (NaDC-1). Objectives: We investigated the expression of NaDC-1 in stone-containing kidneys and evaluated the association of NaDC-1 expression with urine pH. Expression of NaDC-1 protein in acid-treated human proximal renal cells (HK-2 cells) was also studied. Methods: Twenty-four patients with nephrolithiasis aged 50.61 ± 13.30 years (9 males, 15 females) were recruited. Twenty-four hours urine samples were collected from all patients. Expression of NaDC-1 in renal tissues and HK-2 cells was determined by immunohistochemistry and Western blotting, respectively. Results: NaDC-1 was expressed mainly in proximal renal tubular cells. Tubular cells in the medullary region were weakly positive for NaDC-1. The intensity of NaDC-1 expression varied among nephrolithic renal tissues and was categorized into weak (6/24, 25%), intermediate (10/24, 42%), and high (8/24, 33%) expression. A trend of decreased urine pH in patients with increased NaDC-1 expression was observed. When the expression of NaDC-1 was recategorized into low (16/24) and high (8/24) expression, patients with high NaDC-1 expression had significantly lower urine pH than those with low NaDC-1 expression. Acid-treated HK-2 cells (pH 6.8) showed significantly higher expression of NaDC-1 compared with the control nontreated cells (pH 7.4). Significant association between urinary citrate and urine pH was not found. Also, significant association between urinarycitrate and intrarenal NaDC-1 expression was not revealed. Conclusion: NaDC-1 was principally expressed in proximal renal tubules of stone-bearing kidneys. High expression of NaDC-1 was associated with low urine pH. To our knowledge, this is the first report of NaDC-1 expression in the kidneys of nephrolithiasis patients. We experimentally confirmed that acid conditions upregulated theexpression of NaDC-1 in the human proximal tubular cells. Keywords: Acidosis, immunohistochemistry, kidney stone, NaDC-1, nephrolithiasis, sodium-dicarboxylate cotransporter-1, urinary citrate, urine pH

Effect of dietary potassium and anionic salts on acid–base and mineral status in periparturient cows

Dry cow diets based on grassland forage from intensive production contain high amounts of K and could be responsible for a reduced ability to maintain Ca homoeostasis. The aim of this study was to determine whether a moderate anionic salt supplementation to a forage-based pre-calving diet with varying native K content affects the mineral and acid-base status in transition cows. Twenty-four dry and pregnant Holstein cows, without antecedent episodes of clinical hypocalcemia, were assigned to two diets during the last 4 weeks before estimated calving date. Twelve cows were fed a hay-based diet low in K (18 g K/kg DM), and 12, a hay-based diet high in K (35 g K/kg DM). Within each diet, six cows received anionic salts during the last 2 weeks before the estimated calving day. After calving, all cows received the high K diet ad libitum. Blood samples were taken daily from day 11 pre-partum to day 5 post-partum. Urine samples were taken on days 7 and 2 pre-partum and on day 2 post-partum. The anionic salt did not alter feed intake during the pre-partum period. Serum Ca was not influenced by the dietary treatments. Feeding pre-partum diets with low K concentrations induced a reduced metabolic alkalotic charge, as indicated by reduced pre-partum urinary base-acid quotient. Transition cows fed the low K diet including anionic salts induced a mild metabolic acidosis before calving, as indicated by higher urinary Ca, lower urinary pH and net acid-base excretion. Although serum Ca during the post-partum period was not affected by dietary treatment, feeding a low K diet moderately supplemented with anionic salts to reach a dietary cation-anion difference close to zero permitted to obtain a metabolic response in periparturient cows without altering the dry matter intake.

Sulfatides are required for renal adaptation to chronic metabolic acidosis

Urinary ammonium excretion by the kidney is essential for renal excretion of sufficient amounts of protons and to maintain stable blood pH. Ammonium secretion by the collecting duct epithelia accounts for the majority of urinary ammonium; it is driven by an interstitium-to-lumen NH3 gradient due to the accumulation of ammonium in the medullary and papillary interstitium. Here, we demonstrate that sulfatides, highly charged anionic glycosphingolipids, are important for maintaining high papillary ammonium concentration and increased urinary acid elimination during metabolic acidosis. We disrupted sulfatide synthesis by a genetic approach along the entire renal tubule. Renal sulfatide-deficient mice had lower urinary pH accompanied by lower ammonium excretion. Upon acid diet, they showed impaired ammonuria, decreased ammonium accumulation in the papilla, and chronic hyperchloremic metabolic acidosis. Expression levels of ammoniagenic enzymes and Na(+)-K(+)/NH4(+)-2Cl(-) cotransporter 2 were higher, and transepithelial NH3 transport, examined by in vitro microperfusion of cortical and outer medullary collecting ducts, was unaffected in mutant mice. We therefore suggest that sulfatides act as counterions for interstitial ammonium facilitating its retention in the papilla. This study points to a seminal role of sulfatides in renal ammonium handling, urinary acidification, and acid-base homeostasis.

Asupan makan, sindrom metabolik, dan status keseimbangan asam-basa pada lansia

Background: Metabolic syndrome prevalence increases with age and obesity. The metabolic syndrome is associated with alterations in renal function. Low urine pH has been described as a renal manifestation of the metabolic syndrome. Urine pH is a simple and inexpensive method for determining acid-base status. Recent studies suggest that acid-base status is associated with dietary intake.Objective: To examine relationship between dietary intake, components of metabolic syndrome and urine pH among the elderly.Method: Subjects of this cross-sectional study consist of 49 elderly that were collected consecutively. Height, weight, waist circumference (WC), dietary intake, blood pressure (BP), fasting blood glucose and urine were obtained. Rank Spearman correlation test was used to examine the correlation of components of metabolic syndrome and dietary intake with urine pH. Mann-Whitney test was used to compare the urine pH of the metabolic syndrome group and the normal group. Chi-Square/fisher test was used to calculate prevalence ratio (PR) of metabolic syndrome components to low urine pH. Multivariate analysis was done by multiple linear regression.Results: The mean urine pH of the metabolic syndrome group was 6,06 and significantly lower than the normal group (6,50). WC was the only component of metabolic syndrome that related to urine pH (r=-0,325; p=0,023). Abdominal obesity significantly increases the risk of low urine pH (RP=1,6; p=0,023; CI=1,005-2,442). Urine pH was negatively associated with protein intake and proportion of protein on diet. In multivariate analysis, WC is the most significant factor that predicted urinary pH.Conclusion: Urine acidification is a characteristic of abdominal obesity and the metabolic syndrome. Protein intake and proportion of protein on diet contribute to urine pH.

2104 STEATORRHEA AND HYPEROXALURIA OCCUR AFTER RYGB IN DIO RATS REGARDLESS OF DIETARY FAT OR OXALATE

You have accessJournal of UrologyStone Disease: Evaluation & Medical Management (I)1 Apr 20132104 STEATORRHEA AND HYPEROXALURIA OCCUR AFTER RYGB IN DIO RATS REGARDLESS OF DIETARY FAT OR OXALATE Joseph Ellen, M.D. Marguerite Hatch, Ph.D. Saeed Khan, Ph.D. Zach Marmetschke, Bryce Bergeron, and Benjamin CanalesM.D., M.P.H. Joseph EllenJoseph Ellen Gainesville, FL More articles by this author , Marguerite HatchMarguerite Hatch Gainesville, FL More articles by this author , Saeed KhanSaeed Khan Gainesville, FL More articles by this author , Zach MarmetschkeZach Marmetschke Gainesville, FL More articles by this author , Bryce BergeronBryce Bergeron Gainesville, FL More articles by this author , and Benjamin CanalesBenjamin Canales Gainesville, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2013AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Introduction and Objective: Roux-en-Y gastric bypass surgery (RYGB) has been linked to increased post-operative kidney stone risk and hyperoxaluria. Mechanistically, fatty acids are thought to bind intestinal calcium leading to increased unbound oxalate availability and enteric hyperoxaluria. While this hypothesis fits well within oxalate and stone paradigms, clinical malabsorption is uncommonly reported in the RYGB literature. We sought to determine the effect of dietary fat and oxalate on fecal fat excretion and 24 hour urine parameters in a diet-induced obese (DIO) rat model of RYGB surgery with similar weight loss patterns and insulin resistance as humans. METHODS DIO Sprague−Dawley rats underwent sham (Control, n=16) or RYGB (n=19) surgery. Once recovered, animals were fed ad lib normal calcium, high fat (40%) diet with (Ox) or without (No Ox) 1.5% potassium oxalate for 5 weeks then switched to normal (10%) fat diet for 2 weeks. Stool and urine were collected after each period. Fecal fat was determined by gas chromatography, and urine metabolites by assay spectrophotometry. RESULTS Daily % fecal fat excretion in control animals remained extremely low (<5%/day) regardless of dietary fat content. On the contrary, RYGB animals ingested similar food quantity yet had 8-fold higher fecal fat excretion (p<0.001) and heavier stools (p=0.02) than controls. On high fat diet, RYGB Ox had 5-fold increase in urine oxalate excretion (p<0.001) while RYGB No Ox had 2-fold increase in urine calcium (p<0.01) versus controls. Lowering dietary fat in RYGB Ox animals led to a 50% decrease in oxalate excretion (p<0.01), a 30% reduction in urinary calcium (p<0.03), and an increase in urine pH by 0.3 units (p<0.001). CONCLUSIONS In this RYGB model, high fat feeding results in steatorrhea, hyperoxaluria, and low urine pH, partially reversible by lowering dietary fat and oxalate content. However, even on normal fat, no oxalate diet, RYGB rats, compared to controls, excreted twice as much oxalate and could not completely correct for lowered urine pH. Although RYGB hyperoxaluria appears primarily gut and diet-mediated, secondary causes of oxalogenesis from dietary sources, liver metabolism, or other mechanisms deserve further exploration, especially in RYGB patients who report dietary fat and oxalate compliance. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e862-e863 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joseph Ellen Gainesville, FL More articles by this author Marguerite Hatch Gainesville, FL More articles by this author Saeed Khan Gainesville, FL More articles by this author Zach Marmetschke Gainesville, FL More articles by this author Bryce Bergeron Gainesville, FL More articles by this author Benjamin Canales Gainesville, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

2088 HIGHER HEMOGLOBIN A1C IS ASSOCIATED WITH A GREATER LIKELIHOOD OF URIC ACID STONE FORMATION: IS CONTROL OF DIABETES IMPORTANT FOR STONE PREVENTION?

INTRODUCTION AND OBJECTIVES: Patients with diabetes mellitus (DM) are known to have a propensity for lower urine pH and a higher prevalence of uric acid calculi. However, as not all stone forming patients with DM form uric acid stones, other factors may be contributory. Glycemic control in diabetics varies due to factors such as compliance with nutritional, exercise, and pharmacologic regimens. The impact of glycemic control on stone composition, however, is unknown. We examined the influence of hemoglobin A1c (HgbA1c), a measure of long-term DM control, on stone composition. METHODS: Using an approved institutional database, we performed a retrospective chart review of 540 stone formers and extracted clinical characteristics known to be associated with stone formation. We also collected data on DM management and HgbA1c measures to assess glycemic control in diabetics. Patient’s stone types were categorized based both on predominant ( 50%) composition and on the subtype (any uric acid, any brushite, or 5% calcium phosphate). Variables were compared using Fisher’s exact tests and ANOVA. RESULTS: In our cohort, we confirmed that stone formers with DM (n 107) were more likely to have 50% uric acid stones than patients without DM (20% and 5% respectively, p 0.0001) and less likely to have brushite stones (0% in DM, 4% in non-DM, p 0.019). In analyzing subtype stone compositions ( 50%), patients with stones containing any uric acid had higher mean HgbA1c than those with pure CaOx calculi (5.9% vs 6.7%, p 0.02, Figure 1). Patients whose diabetes was managed with oral hypoglycemic medications had more uric acid stones than those managed with other strategies (34% vs 10%, p 0.005) and this may reflect poorer diabetes control in patients prescribed oral medications (mean HgbA1c 7.3% vs 6.2%, p 0.0001). CONCLUSIONS: Our study corroborates others suggesting that diabetic stone formers are more likely to form uric acid stones than the general stone forming population. Uric acid stones should be suspected in patients with DM and especially those with high HgbA1c. Our study suggests that better glycemic control may reduce the likelihood of uric acid nephrolithiasis and supports the inclusion of diabetes control as a component of the multidisciplinary medical management of stone forming patients.

2305 DOES BIOCHEMICAL RISK PROFILE MATCH STONE COMPOSITION FOR CALCIUM OXALATE, URIC ACID, AND MIXED STONE FORMERS?

INTRODUCTION AND OBJECTIVES: Previous studies have demonstrated differences in clinical and biochemical profiles of patients with pure uric acid (UA) and pure calcium oxalate (CaOx) calculi. However, to what degree they differ compared to patients with mixed CaOx/UA calculi is unknown. Therefore, we sought to determine how patients with mixed stone composition compare to the pure stone formers on 24-hour urine analysis. METHODS: We performed a retrospective review of 232 patients with both stone composition analysis and 24 hour urinalysis (Litholink®). Analysis of 24-hour urine constituents across the 3 stone groups (pure UA, pure CaOx and mixed CaOx/UA) was performed using univariable analysis of variance and multivariable linear regression models adjusting for urine volume, creatinine excretion and clinical and demographic factors. RESULTS: A total of 27 (11.6%) patients had mixed CaOx/UA, 122 (52.6%) had pure CaOx and 83 (35.8%) had pure UA calculi. Univariable analysis demonstrated significant differences between mixed CaOx/UA patients and pure CaOx patients for urine pH (mixed 5.63 0.49 vs. pure CaOx 5.93 0.51, p 0.009) and supersaturation (SS) of UA (mixed 1.84 1.09 vs. pure CaOx 1.26 0.93, p 0.01), and a significant difference between mixed CaOx/UA patients and pure UA patients for SS of CaOx (mixed 7.18 4.23 vs. pure UA 4.90 2.96, p 0.005). Multivariable analysis demonstrated that mixed CaOx/UA patients had no significant difference in SS CaOx as compared to pure CaOx patients (difference -0.27, p 0.66), while at the same time had no significant difference in SS UA as compared to pure UA patients (-0.07, p 0.69). Additionally, mixed stone composition patients had significantly lower urinary pH (-0.26, p 0.01) and urinary magnesium (-20.1 mg, p 0.019) than pure CaOx patients; these values were not significantly different that those of pure UA patients. (Table 1). CONCLUSIONS: The biochemical risk profile of patients who form mixed CaOx/UA calculi demonstrated abnormalities that promote both CaOx and UA stone formation. Dietary and medical management for patients with mixed stone composition may require treatment of both defects even if uric acid is the nidus for stone formation in this population.

Steatorrhea and Hyperoxaluria Occur after Gastric Bypass Surgery in Obese Rats Regardless of Dietary Fat or Oxalate

We determined the effect of dietary fat and oxalate on fecal fat excretion and urine parameters in a rat model of Roux-en-Y gastric bypass surgery. Diet induced obese Sprague-Dawley® rats underwent sham surgery as controls (16), or Roux-en-Y gastric bypass surgery (19). After recovery, rats had free access to a normal calcium, high fat (40%) diet with or without 1.5% potassium oxalate for 5 weeks and then a normal (10%) fat diet for 2 weeks. Stool and urine were collected after each period. Fecal fat was determined by gas chromatography and urine metabolites were evaluated by assay spectrophotometry. Daily fecal fat excretion remained low in controls on either diet. However, Roux-en-Y gastric bypass rats ingested a food quantity similar to that of controls but had eightfold higher fecal fat excretion (p <0.001) and heavier stools (p = 0.02). Compared to controls, gastric bypass rats on the high fat diet with potassium oxalate had a fivefold increase in urine oxalate excretion (p <0.001), while gastric bypass rats without potassium oxalate had a twofold increase in urine calcium (p <0.01). Lowering dietary fat in gastric bypass rats with potassium oxalate led to a 50% decrease in oxalate excretion (p <0.01), a 30% decrease in urine calcium and a 0.3 U increase in urine pH (p <0.001). In this Roux-en-Y gastric bypass model high fat feeding resulted in steatorrhea, hyperoxaluria and low urine pH, which were partially reversible by lowering the dietary fat and oxalate content. Roux-en-Y gastric bypass rats on normal fat and no oxalate diets excreted twice as much oxalate as age matched, sham operated controls. Although Roux-en-Y gastric bypass hyperoxaluria appears primarily mediated by gut and diet, secondary causes of oxalogenesis from liver or other mechanisms deserve further exploration.

Accuracy of urine pH testing in a regional metabolic renal clinic: is the dipstick accurate enough?

Urine pH is a useful marker for assessing treatment need and efficacy in patients with nephrolithiasis. Though the gold standard of measurement is with a pH electrode, dipsticks offer the convenience of cost, ease of use, and the possibility of patients measuring their own values outside the clinic. The aim of this study was to determine whether dipsticks offer the same accuracy as the electrode. Paired measurements of freshly voided urine pH with both electrode and dipstick were analysed in a multidisciplinary renal clinic. We found that although there was a high Pearson correlation between the samples (0.89, p = 0.001), urine dipstick measurements carried an approximately 1 in 4 risk of producing clinically significant differences (pH differences > 0.5 pH unit) from meter values. We also found that at high and low urine pH, the dipstick tended to over- and underestimate true pH readings, respectively. Examining the values in the 98 patients where a need for pharmacological urinary pH manipulation was indicated by the true pH, we found 14 who would not have been appropriately treated, and 5 who would have been unnecessarily medicated, if the stick pH value had been used. We conclude that dipstick pH measurement is insufficiently reliable for guiding clinical decision-making.

Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators.

Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation.

Clinical observation of childhood urinary stones induced by melamine-tainted infant formula in Anhui province, China

IntroductionThe current report detailed an investigation of melamine-linked urinary stones in children exposed to contaminated formula.Material and methodsA total of 1062 children fed with melamine-contaminated infant formula were screened for urinary stones. Sixty healthy children without melamine exposure were recruited as a control group. Ultrasonography of the urinary tract system was performed. Urinalysis, renal function, liver status, and serum electrolytes were determined.ResultsWe encountered 49 affected children from the 1062 screened ones, at a rate of 4.6% per ultrasound performed. Thirty-two were male, and 17 were female. The affected children ranged in age from 1 month to 96 months, with a mean of 25 months. Duration of exposure was from 1.3 months to 84 months, with a mean of 19.5 months. The melamine contents in serum were between 12 mg/kg and 2563 mg/kg, with mean concentration of 1295.3 mg/kg. Most affected children were asymptomatic with no urinary findings. Patients with urinary stones exhibited lower urine pH and serum HCO3 – than those in the healthy children, whereas for serum uric acid, alanine aminotransferase, aspartate aminotransferase, and anion gap the opposite trends were observed. The stone diameter ranged from 2 mm to 18 mm with a median of 6.5 mm. Multiple stones were noted in all patients. After 1 week of conservative management, stone diameters of 38 cases (77.6%) were significantly decreased. Among them, urinary stones were discharged completely in 21 affected children (42.9%).ConclusionsThe short-term outcome of melamine-linked urinary stones is satisfactory.

Pathogenesis of Bladder Calculi in the Presence of Urinary Stasis

Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis.

Renal Stone Disease and Obesity: What is Important for Urologists and Nephrologists?

Currently, obesity has reached an epidemic stage and represents a challenge for health authorities across the globe. Certainly, with emergence of obesity epidemic, we started to see an increase in the prevalence of chronic kidney disease (CKD) and nephrolithiasis. Interestingly, epidemiologic studies have shown that the incident stone risk increases with body mass index (BMI), and no further increase in risk is noticed when the BMI > 30 kg/m2. Furthermore, metabolic syndrome and diabetes are also associated with an increase in the incidence of renal stones disease. The shared links between these metabolic disorders are insulin resistance. Furthermore, insulin resistance is thought to alter renal acid–base metabolism, resulting in a lower urine pH and increased risk of uric acid stone disease. Obesity is also associated with excess nutritional intake of lithogenic substances such as refined sugars, low fluid intake, calcium, oxalate, and purine-rich foods. Obesity is also associated with an increase in incidence of urinary tract infection. Recent reports suggested that renal stone disease carries risk of myocardial infarction, progression of CKD, and diabetes. Alarmingly, orlistat (obesity medication) and bariatric surgery are associated with hyperoxaluria and associated stone formation and even oxalate nephropathy. Certainly, the many health risks of obesity, including nephrolithiasis, will add more burden on urologists and nephrologists. Shockwave lithotripsy, percutaneous nephrolithotomy, and ureteroscopy are all safe procedures in obese individuals. Further research is urgently needed to address the pathophysiology and management of obesity-induced renal stones disease.

Comparison of secondary signs as shown by unenhanced helical computed tomography in patients with uric acid or calcium ureteral stones

Unenhanced helical computed tomography (UHCT) has evolved into a well-accepted diagnostic method in patients with suspected ureterolithiasis. UHCT not only shows stones within the lumen of the ureter, it also permits evaluation of the secondary signs associated with ureteral obstruction from stones. However, there we could find no data on how secondary signs might differ in relation to different compositions of ureteral stones. In this study, we compared the degree of secondary signs revealed by UHCT in uric acid stone formers and in patients forming calcium stones. We enrolled 117 patients with ureteral stones who underwent UHCT examination and Fourier transform infra-red analysis of stone samples. Clinical data were collected as follows: age, sex, estimated glomerular filtration rate (eGFR), urine pH, and radiological data on secondary signs apparent on UHCT. The uric acid stone formers had significantly lower urine pH and eGFR in comparison to calcium stone formers, and on UHCT they also had a higher percentage of the secondary signs, including rim sign (78.9% vs. 60.2%), hydroureter (94.7% vs. 89.8%), perirenal stranding (84.2% vs. 59.2%) and kidney density difference (73.7% vs. 50.0%). The radiological difference was statistically significant for perirenal stranding (p=0.041). In conclusion, we found that UHCT scanning reveals secondary signs to be more frequent in patients with uric acid ureteral stones than in patients with calcium stones, a tendency that might result from an acidic urine environment.

Obesity and stones

With all the attention to the epidemic of obesity in children today, little attention has been paid to a less obvious “epidemic”: kidney stones. Once largely a condition of adults (or children with unusual underlying conditions), urolithiasis is becoming a much more frequently made diagnosis in pediatric nephrology and urology practices. There has been a suggestion that the two conditions could somehow be linked. There are a number of metabolic conditions that are known to predispose to urolithiasis. In this issue of The Journal, Tiwari et al studied 46 obese adolescents to determine if they had an increased number of known risk factors for urinary stone formation. Indeed, they did. The relative saturation of calcium oxalate, a measure of the likelihood of precipitation of the most common minerals in renal stones, was elevated in the group as a whole, and the degree of elevation was correlated with the number of metabolic syndrome risk factors. Another stone-formation risk factor, low urine pH, was similarly correlated with metabolic syndrome risk factors. Although this is a preliminary study, and is somewhat at odds with existing studies in adults, it serves to draw our attention to the fact that the consequences of overweight in children extend beyond the obvious cardiovascular complications. Article page 615▶ Metabolic Syndrome in Obese Adolescents is Associated with Risk for NephrolithiasisThe Journal of PediatricsVol. 160Issue 4PreviewTo examine the relationship between urinary pH and metabolic syndrome risk factors along with insulin resistance in obese adolescents, and to evaluate the relationship between other urinary stone-forming and -inhibiting markers and metabolic syndrome. Full-Text PDF

Urinary Stone Formers with Hypocitraturia and ‘Normal’ Urinary pH Are at High Risk for Recurrence

Background: Citrate is one of the most important inhibitors in urolithiasis. Hypocitraturia is a common risk factor in stone formers. Citrate excretion is regulated – amongst others – by acidosis and protein intake. A considerable number of stone formers, however, show hypocitraturia in the presence of normal urine pH levels. This is potentially due to defects in the renal tubular citrate carriers (NaDC 1 and 3) which may be genetically determined. Patients and Methods: 350 consecutive stone formers were examined. Exclusion criteria were urinary tract infection, hypokalemia, and steatorrhea. The following parameters were measured: serum: creatinine, calcium, potassium, and uric acid; urine: pH profiles, citrate, calcium, uric acid, ammonia, urea, and creatinine. Results: 83/350 patients were hypocitraturic (48 males, 35 females). 14/83 had low urine pH (≤6), 69/83 showed normal levels (>6). In the latter group there was a significantly higher recurrence rate (23 vs. 9%). The two groups were not different in serum parameters apart from uric acid. In urine, only pH and calcium (males) were significantly lower in the first group. Citrate did not correlate with urine pH and creatinine in the hypocitraturia-normal pH group, only with calcium in both sexes and urea and ammonia in females. In the hypocitraturia-low pH patients, there was no significant correlation between citrate and any other parameter tested. Conclusions: Hypocitraturia with normal urine pH is an entity indicating a high risk for recurrence. Since there was no correlation between citrate and pH, urea and ammonia, respectively, citrate excretion is not regulated in these patients as usual. There may be a link to calcium excretion. Potentially, these patients have defects in the renal tubular citrate carriers which may be genetically determined. Genetic examinations should be performed to elucidate a potential genetic disorder in hypocitraturia-normal pH stone formers.

Current ideas on the pathogenesis of uric acid nephrolithiasis and its correction methods in gouty patients

output The paper describes current ideas on the pathogenesis and treatment of nephrolithiasis, virtually a constant attendant of gout. The prevalence of nephrolithiasis is reported to be increasing worldwide. Among all cases of nephrolithiasis, the frequency of uric acid nephrolithiasis ranges from 5 to 40%; that of nephrolithiasis in gout is, according to the data by different authors, 7 to 10%. Hyperuricosuria, low urine volume, and low urine pH are considered to be classical risk factors for uric acid nephrolithiasis. Uric acid nephrolithiasis, including that in gout, even if asymptomatic, is noted to require active therapy. The paper presents the basic principles of treatment for uric acid nephrolithiasis: to normalize urine pH; to eliminate or neutralize the sequels of hyperuricosuria, to correct comorbidities, and to increase urine.

Protein intake, calcium balance and health consequences

High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.

Beware the low urine pH—the major cause of the increased prevalence of nephrolithiasis in the patient with type 2 diabetes

There is an increased prevalence of nephrolithiasis and an increase in the incidence of renal colic in patients with diabetes, obesity, hypertension and insulin resistance because of an increased frequency of uric acid crystallization. Uric acid crystallization occurs in the milieu of an acid urine and is not due to hyperuricosuria as with insulin resistance, urinary uric acid levels are generally decreased because of increased renal tubular reabsorption. However, in the presence of insulin resistance, there is decreased renal tubular generation of ammonia and increased sodium absorption leading to acidification of the urine and uric acid crystallization. The presence of a low urine pH should alert the clinician to the increased risk of nephrolithiasis particularly in the obese, diabetic or hypertensive patient. Prevention of nephrolithiasis can be achieved in susceptible individuals either by alkalizing the urine and/or by further decreasing the uric acid content of the urine with a xanthine oxidase inhibitor such as allopurinol.