Urinary pH In Patients Research Articles

Urinary Citrate Levels Do Not Correlate with Urinary pH in Patients with Urinary Stone Formation

Urinary excretion of citrate is dependent on glomerular filtration, tubular reabsorption, and excretion. Acid base status is thought to play a significant role in urinary citrate excretion. It has been assumed that increased urinary citrate will increase urinary pH. The aim of this study was to confirm the association of increased urinary citrate levels with increased urinary pH. The 24-hour urine collections of all patients with stones referred to our clinic in the past 4 years were reviewed. The samples were collected and analyzed for routine stone risk profiles by a commercial laboratory (Litholink, Chicago, Ill). The Student t test and analysis of variance were used to compare the mean values as applicable. Pearson's correlations were also calculated for each variable. A total of 572 patients had at least one 24-hour urine sample from the past 4 years. The mean urinary citrate was 305 mg/day. The mean urinary pH of all patients was 6.14. Statistical evaluation of all patients showed no correlation between urinary citrate and pH (r = -0.04, P = 0.36). In a subset of patients with urinary potassium greater than 100 mEq/day (n = 100), urinary citrate and urinary pH were both increased; however, there was still no correlation between the two (r = 0.011, P = 0.806). Despite the current dogma that increasing urinary citrate increases urinary pH, in a cohort of patients with urinary stone formation who provided 24-hour urine specimens, no correlation was found between urinary citrate and urinary pH levels.

Relationship between Insulin Resistance and Low Urinary pH in Patients with Gout, and Effects of PPARα Agonists on Urine pH

Patients with gout frequently have low urinary pH, though the underlying mechanism has not been identified. Recently, nephrolithiasis has been reported to be involved with renal manifestation of metabolic syndrome. The present study was conducted to clarify the mechanism of low urinary pH in gout patients. The relationships between urine pH and factors contributing to metabolic syndrome were investigated. In addition, the effects of PPAR alpha agonists on urine pH were examined. Patients with 24-hour urine samples below a level of pH 5.5 showed higher values for factors constituting metabolic syndrome, compared with those with 24-hour urine pH equal to or greater than 5.5. Multiple regression analysis demonstrated that HOMA index was the only contributing factor to low urinary pH in gout patients, except for serum uric acid. Administrations of PPAR alpha agonists significantly raised 24-hour urine pH levels in gout patients in accordance with a reduction in serum triglyceride concentration, probably through their activities to improve insulin resistance. Our results suggest that insulin resistance plays an important role in the development of low urinary pH in patients with gout and that PPAR alpha agonist is preferable for raising urinary pH of the gout patients with hypertriglyceridemia.

Studies to identify the basis for an alkaline urine pH in patients with calcium hydrogen phosphate kidney stones

Patients with CaHPO(4) kidney stones belong to a diagnostic category that has a high urine pH as its common feature. Our objective was to provide a new clinical approach to examine the basis for this high pH. The study group consisted of 26 CaHPO(4) stone formers and 28 normal volunteers. Urine was collected q2h plus an overnight sample to identify patients with a urine pH > 6.5 for 12/24 h. Urine ammonium (U(NH4)), sulphate (U(SO4)) and citrate were measured and diet net alkali was calculated. Of the 26 patients, 13 had persistently alkaline urine. In 7/13, U(NH4) (68 +/- 13 mEq/day) and U(SO4) (57 +/- 7 mEq/day) were both high. In 6/13 patients, U(NH4) was the usual 31 +/- 3 mEq/day; in 4/6, U(NH4)/U(SO4) was 0.9 +/- 0.1; the cause of the alkaline urine pH seemed to be a dietary alkali load because the rise in urine pH was episodic and coincided with a high net diet alkali load and peak citrate excretion rates. The remaining two patients had a high U(NH4)/U(SO4) (2.2 and 1.6). Citrate excretion was very low in the male, but not in the female patient. There are heterogeneous causes for a persistently high urine pH. Two of the patients had a possible molecular basis: the lesion could be a low proximal convoluted tubule cell pH in the male and an increased entry of NH(3) into the late distal nephron in the female.

Urine Composition in Type 2 Diabetes

Type 2 diabetes is a risk factor for nephrolithiasis in general and has been associated with uric acid stones in particular. The purpose of this study was to identify the metabolic features that place patients with type 2 diabetes at increased risk for uric acid nephrolithiasis. Three groups of individuals were recruited for this outpatient study: patients who have type 2 diabetes and are not stone formers (n = 24), patients who do not have diabetes and are uric acid stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants provided a fasting blood sample and a single 24-h urine collection for stone risk analysis. Twenty-four-hour urine volume and total uric acid did not differ among the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH than NV. Urine pH inversely correlated with both body weight and 24-h urine sulfate in all groups. Urine pH remained significantly lower in patients with type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate (P < 0.01). For a given urine sulfate, urine net acid excretion tended to be higher in patients with type 2 diabetes versus NV. With increasing urine sulfate, NV and patients with type 2 diabetes had a similar rise in urine ammonium, whereas in UASF, ammonium excretion remained unchanged. The main risk factor for uric acid nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body mass and increased acid intake can contribute to but cannot entirely account for the lower urine pH in patients with type 2 diabetes.

Effect of a phosphate supplement on urine pH in patients with neurogenic bladder receiving intermittent catheterization

Pilot study; prospective design. University Hospital, Virginia, USA. To examine a phosphorus supplement as a urine-acidifying agent in patients with neurogenic bladder on clean intermittent catheterization. Seven patients were followed for 4 weeks. For the first week of study urine pH was measured three times a day: first morning urine sample, afternoon sample, evening sample. For the second and third weeks urine pH was measured and the patients drank a phosphorus supplement three times a day. For the fourth week of study the patients did not take the phosphorus supplement but the measurement of urine pH was continued. The patients were visited in their homes twice a week. During each visit a sample of urine was collected for culture. A supplement container count was performed and urine pH recordings were checked. There was no significant change in urine pH during the 2-week period when a patient was on phosphorus supplementation compared to when the patient was off supplementation. In addition, urine acidification was not achieved over the time period when urine pH was monitored. Phosphate supplementation had no effect on urine pH in patients with neurogenic bladder.

The metabolic syndrome and uric acid nephrolithiasis: Novel features of renal manifestation of insulin resistance

Uric acid nephrolithiasis primarily results from low urinary pH, which increases the concentration of the insoluble undissociated uric acid, causing formation of both uric acid and mixed uric acid/calcium oxalate stones. These patients have recently been described as exhibiting features of insulin resistance. This study was designed to evaluate if insulin resistance is associated with excessively low urinary pH in overtly healthy volunteers (non-stone formers) and if insulin resistance may explain the excessively low urinary pH in patients with uric acid nephrolithiasis. Fifty-five healthy volunteers (non stone-formers) with a large range of body mass index and 13 patients with recurrent uric acid nephrolithiasis underwent hyperinsulinemic euglycemic clamp, 24-hour urinary studies, and anthropometric measurements of adiposity. A subgroup of 35 non-stone formers had 2-hour timed urinary collection before and during the hyperinsulinemic phase of the clamp studies. For the non-stone former population, low insulin sensitivity measured as glucose disposal rate significantly correlated with low 24-hour urinary pH (r= 0. 35; P= 0.01). In addition to the previously described acidic urine pH and hypouricosuria, patients with recurrent uric acid nephrolithiasis were found to be severely insulin resistant (glucose disposal rate: uric acid stone-formers vs. normals; 4.1 +/- 1.3 vs. 6.9 +/- 2.1 mg/min/kg of lean body mass, P= 0.008). Acute hyperinsulinemia was associated with higher urinary pH (6.1 +/- 0.7 at baseline to 6.8 +/- 0.7 during hyperinsulinemia; P < 0.0001), urinary ammonia excretion (2.7 +/- 1.6 mEq/2 hr at baseline and 4.0 +/- 2.6 mEq/2 hr P= 0.002) and urinary citrate excretion (48 +/- 33 mg/2 hr at baseline and 113 +/- 68 mg/2 hr P < 0.0001). We conclude that one renal manifestation of insulin resistance may be low urinary ammonium and pH. This defect can result in increased risk of uric acid precipitation despite normouricosuria.

Biochemical profile of stone-forming patients with diabetes mellitus

Objectives To test the hypothesis that stone-forming patients with type II diabetes (DM-II) have a high prevalence of uric acid (UA) stones and present with some of the biochemical features of gouty diathesis (GD). Methods The demographic and initial biochemical data from 59 stone-forming patients with DM-II (serum glucose greater than 126 mg/dL, no insulin therapy, older than 35 years of age) from Dallas, Texas and Durham, North Carolina were retrieved and compared with data from 58 patients with GD and 116 with hyperuricosuric calcium oxalate urolithiasis (HUCU) without DM. Results UA stones were detected in 33.9% of patients with DM-II compared with 6.2% of stone-forming patients without DM ( P <0.001). Despite similar ingestion of alkali, the urinary pH in patients with DM-II and UA stones (n = 20) was low (pH = 5.5), as it is in patients with GD, and was significantly lower than in patients with HUCU. The urinary pH in patients with DM-II and calcium stones (n = 39) was intermediate between that in those with DM-II and UA stones and those with HUCU. However, both DM groups had fractional excretion of urate that was not depressed, as it is in those with GD, and was comparable to the value obtained in those with HUCU. The urinary content of undissociated UA was significantly higher, and the saturation of calcium phosphate (brushite) and sodium urate was significantly lower in those with DM-II and UA stones than in those with HUCU. Conclusions Stone-forming patients with DM-II have a high prevalence of UA stones. Diabetic patients with UA stones share a key feature of those with GD, namely the passage of unusually acid urine, but not the low fractional excretion of urate.

Studies on the pathophysiology of the low urine pH in patients with uric acid stones

A very low urine pH is the major risk factor for uric acid stone formation. A subgroup of patients with a history of uric acid stones and a persistently low urine pH (<5.5 for at least 12 h/day) were selected for detailed study. Based on their relative ammonium (NH(+)(4)) and sulfate (SO(2-)(4)) excretions, patients were divided into two groups. The first group (N = 2) excreted 173 and 139% more NH(+)(4) than SO(2-)(4). Their daily urinary unmeasured anion excretion was higher than their calculated net diet alkali input (38 and 61 vs. 24 and 49 mEq, respectively). In the second group (N = 12), NH(+)(4) excretion was 69 +/- 5% that of SO(2-)(4). In 2 of 12, decreased renal ammoniagenesis was suspected due to a plasma potassium of 5.3 mmol/L and/or a lower GFR (65 and 59 L/day); these patients had an extremely low citrate excretion (3 and 1 mEq/day). In contrast, citrate excretion was not low in the remaining 10 patients (10.4 +/- 1.3 mEq/day). Patients in group 1 needed a higher NH(+)(4) excretion possibly because of a H+ load from excessive renal excretion of organic anions. We speculate that an alkaline proximal tubular cell pH could be the basis for the low NH(+)(4) and high citrate excretions in 10 of 12 patients in group 2. Dietary factors and/or a molecular lesion may contribute to their pathophysiology.

Magnesium Hydrogen Carbonate Natural Mineral Water Enriched with K+-Citrate and Vitamin B6 Improves Urinary Abnormalities in Patients with Calcium Oxalate Nephrolithiasis

The influence of drinking magnesium hydrogen carbonate natural mineral water enriched with potassium citrate on urinary metabolic abnormalities was prospectively studied in 27 patients with recurrent calcium oxalate nephrolithiasis. The mean 24-hour urinary pH shifted from 6.34 to 6.93 (p < 0.01), the mean urinary magnesium/urinary creatinine ratio rose from 0.47 to 0.67 (p < 0.01), the mean urinary citrate/urinary creatinine ratio increased from 0.26 to 0.35 (p NS), and the mean 24-hour urinary calcium decreased from 7.98 to 6.05 mmol (p < 0.05). The effects of magnesium hydrogen carbonate natural mineral water enriched with potassium citrate were found to be favorable on urinary calcium, urinary magnesium/urinary creatinine ratio and urinary pH in patients with calcium oxalate nephrolithiasis.

The spectrum of endemic renal tubular acidosis in the northeast of Thailand.

We have previously reported a high prevalence of endemic renal tubular acidosis (EnRTA) in the northeast of Thailand, and our subsequent studies provided evidence that K deficiency exists in the same region. Since tubulointerstitial damage is associated with K deficiency, we postulate that this might be implicated in the pathogenesis of EnRTA and, if so, that a spectrum of tubulointerstitial abnormalities can be anticipated. In this study we evaluated renal acidification ability in 4 patients and in 11 of their relatives. We used a 3-day acid load (NH4Cl 0.1 g/kg/day) followed by 20 mg oral furosemide and monitored the maximal renal concentrating ability using water deprivation and intranasal 1-deamino-D-arginine vasopressin. The results showed that the subjects could be divided into three groups; normal relatives of the patients, those with suspected renal tubular acidosis, and patients with overt EnRTA who had chronic metabolic acidosis and a low rate of excretion of NH4+. The rate of excretion of K was very low (20 +/- 4 mmol/day) in patients with EnRTA and in their relatives with suspected EnRTA. The transtubular K concentration gradient was also very low in their relatives, especially in patients with suspected EnRTA (2.8 +/- 0.2). With a 3-day NH4Cl load, the rate of excretion of NH4+ was very low in patients with EnRTA (32 +/- 9 mmol/day), and the relatives with suspected EnRTA also had a decreased capacity to excrete NH+4 (50 +/- 14 mmol/day). In contrast, the normal relatives excreted 92 +/- 12 mmol of NH+4/day. The patients with EnRTA could lower their urine pH to less than 5.5 after the acid loading (6.2 +/- 0.3). After furosemide (20 mg), the NH4+ excretion in the patients with EnRTA was lower than in the normal relatives. Moreover, the minimum urine pH in patients with EnRTA did not fall (6.1 +/- 0.2), but there was a fall to 4.8 +/- 0.1 in the patients with suspected EnRTA after furosemide treatment. In conclusion, there was a spectrum of tubulointerstitial abnormalities ranging from suspected to overt distal RTA in a geographic area known to have a high prevalence of K deficiency. K deficiency might be the important pathogenetic factor of EnRTA in the northeast of Thailand.

Distal nephron function in patients receiving chronic lithium therapy

Renal tubular function was studied in 14 patients chronically treated with lithium for affective disorders. Patients were separated into two groups according to the duration of lithium therapy: long-term (35 +/- 7.0 months) and short-term (4.8 +/- 0.8 months). At comparable urine lithium concentrations, patients on long-term therapy had a lower maximal urine osmolality (Umax) and free water reabsorption (TcH2O) than did patients on short-term therapy. The latter group achieved a Umax above 800 mOsm kg H2O. In contrast, both groups of patients failed to increase the urine-blood (U-B) Pco2 gradient normally during acute sodium bicarbonate loading. This low U-B Pco2 was observed at comparable urine bicarbonate concentrations between both groups of patients and controls, and thus was associated with a higher urine pH in patients. These findings indicate that the inability of these patients to achieve a normal U-B Pco2 in a maximally alkaline urine was the result of decreased distal hydrogen ion secretion rather than inability to raise urine bicarbonate concentrations as a result of a concentrating defect. Bicarbonate reabsorptive capacity was normal in our lithium-treated subjects. Both groups of patients achieved a normal U-B Pco2 gradient in response to sodium phosphate loading. They also were able to achieve a minimal urine pH and a maximal acid excretion similar to those of controls in response to a 3-day ammonium chloride loading test. Our data demonstrate that chronic lithium therapy is associated with a mild distal acidification defect disclosed only by the finding of a low U-B Pco2 gradient during sodium bicarbonate loading. This peculiar defect can be found in short-term lithium-treated patients in whom the concentrating capacity is relatively well preserved.

Effect of ascorbic acid on urine pH in patients with injured spinal cords

The ability of ascorbic acid to lower urinary pH in patients with spinal cord injury and neurogenic bladder was studied. Ascorbic acid (1 g four times daily) or placebo was administered for five days in a double-blind, crossover study to 20 patients with spinal cord injury and neurogenic bladder. Urine pH was measured for two days before and during administration of placebo or ascorbic acid. The mean decrease in urinary pH with ascorbic acid was 0.58, but this reduction was not statistically or clinically significant. Only 7 of 20 patients showed a mean urine pH of 5.5 or less (acidic) during treatment with ascorbic acid. The study suggests that an ascorbic acid dosage of 1 g four times daily should not be used to maintain an acidic urinary pH for control of urinary tract infections in patients with spinal cord injuries.

Urinary Lithogenesis in Sudanese Patients: A Study on 125 Stone Formers

This prospective study confirms the previously reported high incidence of uric acid lithiasis in the Sudan. Despite this fact urinary pH in patients in whom stones formed was not significantly different from controls (p>0.05). However, a significantly high serum uric acid level (p <0.01) was associated with recurrent and/or bilateral stones. In patients with single episodes of stones significant hyponatremia (p <0.001) may indicate excessive sweating. The resulting low urine output supersaturated with crystals may explain lithogenesis in this group of patients.