Monophosphoryl lipid A prevents impairment of medullary thick ascending limb [Formula: see text] absorption and improves plasma [Formula: see text] concentration in septic mice.

Metabolic acidosis is the most common acid-base disorder in septic patients and is associated with increased mortality. Previously, we demonstrated that sepsis induced by cecal ligation and puncture (CLP) impairs [Formula: see text] absorption in the medullary thick ascending limb (MTAL) by 1) decreasing the intrinsic [Formula: see text] absorptive capacity and 2) enhancing inhibition of [Formula: see text] absorption by LPS through upregulation of Toll-like receptor (TLR) 4 signaling. Both effects depend on ERK activation. Monophosphoryl lipid A (MPLA) is a detoxified TLR4 agonist that enhances innate antimicrobial immunity and improves survival following sepsis. Pretreatment of MTALs with MPLA in vitro prevents LPS inhibition of [Formula: see text] absorption. Here we examined whether pretreatment with MPLA would protect the MTAL against sepsis. Vehicle or MPLA was administered to mice 48 h before sham or CLP surgery, and MTALs were studied in vitro 18 h postsurgery. Pretreatment with MPLA prevented the effects of sepsis to decrease the basal [Formula: see text] absorption rate and enhance inhibition by LPS. These protective effects were mediated through MPLA stimulation of a Toll/IL-1 receptor domain-containing adaptor-inducing IFN-ß-(TRIF)-dependent phosphatidylinositol 3-kinase-Akt pathway that prevents sepsis- and LPS-induced ERK activation. The effects of MPLA to improve MTAL [Formula: see text] absorption were associated with marked improvement in plasma [Formula: see text] concentration, supporting a role for the kidneys in the pathogenesis of sepsis-induced metabolic acidosis. These studies support detoxified TLR4-based immunomodulators, such as MPLA, that enhance antimicrobial responses as a safe and effective approach to prevent or treat sepsis-induced renal tubule dysfunction and identify cell signaling pathways that can be targeted to preserve MTAL [Formula: see text] absorption and attenuate metabolic acidosis during sepsis.

Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule.

Na(+)-glucose cotransporter 1 (SGLT1)-mediated glucose uptake leads to activation of Na(+)-H(+) exchanger 3 (NHE3) in the intestine by a process that is not dependent on glucose metabolism. This coactivation may be important for postprandial nutrient uptake. However, it remains to be determined whether SGLT-mediated glucose uptake regulates NHE3-mediated NaHCO3 reabsorption in the renal proximal tubule. Considering that this nephron segment also expresses SGLT2 and that the kidneys and intestine show significant variations in daily glucose availability, the goal of this study was to determine the effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule. Stationary in vivo microperfusion experiments showed that luminal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption. This stimulatory effect was mediated by glycolytic metabolism but not through ATP production. Conversely, luminal perfusion with 40 mM glucose inhibited NHE3 because of cell swelling. Notably, pharmacologic inhibition of SGLT activity by Phlorizin produced a marked inhibition of NHE3, even in the absence of glucose. Furthermore, immunofluorescence experiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat renal proximal tubule. Collectively, these findings show that glucose exerts a bimodal effect on NHE3. The physiologic metabolism of glucose stimulates NHE3 transport activity, whereas, supraphysiologic glucose concentrations inhibit this exchanger. Additionally, Phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule.

Alkaline mineral water lowers bone resorption even in calcium sufficiency: alkaline mineral water and bone metabolism.

BACKGROUND: Dietary acid charge enhances bone loss. Bicarbonate or alkali diet decreases bone resorption in humans. We compared the effect of an alkaline mineral water, rich in bicarbonate, with that of an acid one, rich in calcium only, on bone markers, in young women with a normal calcium intake. METHODS: This study compared water A (per litre: 520 mg Ca, 291 mg HCO(3)(-), 1160 mg SO(4)(-), Potential Renal Acid load (PRAL) +9.2 mEq) with water B (per litre: 547 mg Ca, 2172 mg HCO(3)(-), 9 mg SO(4)(-), PRAL -11.2 mEq). 30 female dieticians aged 26.3 yrs (SD 7.3) were randomized into two groups, followed an identical weighed, balanced diet (965 mg Ca) and drank 1.5 l/d of the assigned water. Changes in blood and urine electrolytes, C-telopeptides (CTX), urinary pH and bicarbonate, and serum PTH were measured after 2 and 4 weeks. RESULTS: The two groups were not different at baseline, and showed a similar increase in urinary calcium excretion. Urinary pH and bicarbonate excretion increased with water B, but not with water A. PTH (p=0.022) and S-CTX (p=0.023) decreased with water B but not with water A. CONCLUSION: In calcium sufficiency, the acid calcium-rich water had no effect on bone resorption, while the alkaline water rich in bicarbonate led to a significant decrease of PTH and of S-CTX.

Renal tubular acidosis type 2 with Fanconi's syndrome, osteomalacia, osteoporosis, and secondary hyperaldosteronism in an adult consequent to vitamin D and calcium deficiency: effect of vitamin D and calcium citrate therapy.

OBJECTIVE: To describe a unique example of renal tubular acidosis type 2 (RTA 2) in conjunction with Fanconi's syndrome and osteomalacia consequent to vitamin D and calcium deficiency in an adult without underlying gastrointestinal disease. METHODS: We review the clinical, hormonal, histomorphometric, and micro-computed tomographic findings and the response to therapy with vitamin D and calcium in our patient. RESULTS: On admission, a 33-year-old African American woman had the following laboratory findings: serum ionized calcium 3.8 mg/dL (0.95 mmol/L), venous pH 7.26, bicarbonate 20 mEq/L, chloride 111 mEq/L, alkaline phosphatase 1,192 U/L (20.26 microkat/L) (normal, 40 to 136 U/L), 25-hydroxyvitamin D <5 ng/mL (<12 nmol/L) (normal, 10 to 60 ng/mL), parathyroid hormone 1,620 pg/mL (165.2 pmol/L) (normal, 10 to 60 pg/mL), aldosterone 68.4 ng/dL (1,894.7 pmol/L) (normal, 4.5 to 35.4 ng/dL), supine plasma renin activity 19.8 ng/mL per hour (5.35 ng/L per second) (normal, 0.5 to 1.8 ng/mL per hour), and aminoaciduria. A lumbar spine bone density T-score was -4.6, and a femoral neck T-score was -4.9. An undecalcified tetracycline-labeled bone biopsy specimen showed severe osteomalacia, severe osteoporosis, and peritrabecular fibrosis. A small intestinal biopsy revealed normal findings. Results of an ammonium chloride loading test and a bicarbonate infusion test were consistent with RTA 2. After 24 months of vitamin D and calcium therapy, results of serum and urine chemistry studies and bicarbonate infusion normalized. The lumbar spine T-score improved to -2.0, and the femoral neck T-score improved to -2.7. Bone biopsy specimens demonstrated resolution of the osteomalacia. CONCLUSION: Nutritional vitamin D and calcium deficiency may cause RTA 2, Fanconi's syndrome, and osteomalacia in adults as well as in children.

Toxicity and carcinogenicity of acidogenic or alkalogenic diets in rats; effects of feeding NH(4)Cl, KHCO(3) or KCl.

The effects of diet-induced acid-base disturbances were examined in 4-week, 13-week and 18-month toxicity studies, and in a 30-month carcinogenicity study. Rats were fed a natural ingredient diet (controls), supplemented with 2% or 4% KHCO(3) (base-forming diets), or with 1% or 2.1% NH(4)Cl (acid-forming diets). Additional controls were fed 3% KCl (neutral diet providing K(+) and Cl(-) in amounts equimolar to those in the 4% KHCO(3) diet and the 2.1% NH(4)Cl diet, respectively). NH(4)Cl induced the expected metabolic acidosis, as shown by decreased base excess in blood, decreased urinary pH and increased urinary net acid excretion. KHCO(3) induced the opposite effects. KCl did not affect the acid-base balance. Clinical condition and death rate were not affected. The feeding of high levels of each salt resulted in growth retardation and increased water intake and urinary volume. Plasma potassium and urinary potassium excretion were increased with KHCO(3) and KCl. Plasma chloride was increased with NH(4)Cl, but not with KCl. Urinary calcium and phosphate excretion were increased with NH(4)Cl, but there were no indications that bone minerals were involved (weight, calcium content and fat free solid of the femur were not affected). Standard haematological and clinical chemistry parameters were not affected. Kidney weights were increased with 2.1% NH(4)Cl. Hypertrophy of the adrenal zona glomerulosa occurred with KHCO(3), KCl and NH(4)Cl, due to chronic stimulation of the adrenal cortex by either K(+) or by NH(4)Cl-induced acidosis. An early onset (from week 13) of oncocytic tubules was noted in the kidneys of rats fed KHCO(3) and, after 30 months, the incidence of this lesion was much higher than the background incidence in ageing controls. No progression to oncocytomas was noted. KCl showed only slight effects on the early onset of oncocytic tubules (from 18 months). In contrast, the severity of nephrosis and the incidence of oncocytic tubules were decreased with 2.1% NH(4)Cl, suggesting a protective effect of acidosis. The feeding of KHCO(3) resulted in hyperplasia, papillomas and carcinomas of the urinary bladder. With KCl only a slight increase in proliferative urothelial lesions was noted. Apart from these (pre-)neoplastic lesions in the urinary bladder there were no treatment-related differences in tumour response among the groups. We concluded that most of the observed changes represent physiological adaptations to the feeding of acid- or base-forming salts. Remarkable effects noted with KHCO(3), and to a far lesser extent with KCl, consisted of renal oncocytic tubules and (pre-)neoplastic lesions of the urinary bladder epithelium. NH(4)Cl-induced chronic metabolic acidosis was not associated with dissolution of alkaline bone salts in rats. Finally, a protective effect of chronic acidosis on tumour development was not found.

Bicarbonate reabsorption and NHE-3 expression: abundance and activity are increased in Henle's loop of remnant rats.

BACKGROUND: The bulk of bicarbonate reabsorption along the loop of Henle (LOH) is localized at the level of the thick ascending limb (TAL) and is mainly dependent on the presence of luminal Na+-H+ exchanger (NHE-3). We investigated whether the reduction of renal mass is associated with alterations in LOH bicarbonate transport coupled to changes in NHE-3 gene expression and in vivo activity. METHODS: Sham-operated and remnant rats (4/6 nephrectomy) were studied 15 days after the surgery. To measure net bicarbonate reabsorption (JHCO3-) superficial loops were perfused by in vivo micropuncture. Perfusate was an end-like proximal solution containing 3H-methoxy-inulin. NHE-3 gene expression was quantified by competitive PCR using an internal standard of cDNA that differed from the wild-type NHE-3 by a deletion of 76 bp. Western blot experiments were performed on TAL suspension using anti-NHE-3 antibodies. RESULTS: At various LOH bicarbonate loads, JHCO3- was constantly larger in remnant rats as compared to sham-operated animals. NHE-3 mRNA abundance was estimated to be 0.339 +/- 0.031 attomoles (amol)/ng-1 total RNA in sham-operated (N = 5) and it increased to 0.465 +/- 0.023 in remnant rats (N = 5, P < 0.01). Western blot experiments showed a significant increase of NHE-3 protein abundance in TAL of remnant rats as compared to sham-operated animals. Finally, by means of a specific NHE-3 inhibitor, S-3226, in vivo microperfusion experiments demonstrated that NHE-3 in vivo activity along the LOH was substantially increased in remnant rats in addition to the non-NHE-3 bicarbonate transport. CONCLUSIONS: These data indicate that the reduction of renal mass increases mRNA, protein abundance and in vivo activity of NHE-3 along the TAL. This may explain, at least in part, the augmented transepithelial bicarbonate transport along the LOH. Such an effect will counterbalance the increased glomerular bicarbonate load, thus preventing urinary bicarbonate loss and mitigating the ensuing metabolic acidosis.

5-Aminosalicylic acid-associated renal tubular acidosis with decreased renal function in Crohn's disease.

The use of 5-aminosalicylic acid (5-ASA, mesalazine) in Crohn's disease is usually well tolerated. Nevertheless, the occasional occurrence of nephrotoxic side effects has been described in several case reports. We present the case of a 34-year-old female in whom chronic use of 5-ASA may have caused renal damage which manifested with tubular acidosis, severe weight loss, shortness of breath and fatigue. For 17 years the patient has suffered from Crohn's disease. She received sulfasalazine (3 g/day) for 12 years and was treated with resin-coated mesalazine (3 g/day) for the last 72 months. Onset of weight loss of 10 kg over a 6-month period, accompanied by progressive shortness of breath and fatigue, lead to a diagnosis of metabolic acidosis and renal bicarbonate loss due to damage to the tubular epithelium. Kidney biopsy demonstrated acute interstitial nephritis which may be related to 5-ASA.

Renal tubular disorders and arteriopathy of the lower limbs: risk factors for osteoporosis in men?

In order to clarify the risk-factors for men with vertebral fractures due to osteoporosis, we carried out a study of 51 cases. Twenty-five percent of patients had an endocrine disorder (hyperparathyroidism, hypogonadism, hyperthyroidism) or had received corticosteroids. These patients were compared with 26 age-matched controls. Eleven patients compared with 2 of the 26 control subjects had arteriopathy of the lower limbs; 11 patients had hypercalciuria or hyperphosphaturia compared with 3 of the control subjects. Arteriopathy appears to be associated with osteoporosis in older patients (mean age 71 years), whereas renal tubular disorders were found in younger patients (mean age 45 years).

Renal ammonia in autosomal dominant polycystic kidney disease.

Recent studies have suggested that defective medullary trapping of ammonia underlies the acidosis associated with renal failure and sets in motion maladaptive compensatory mechanisms that contribute to the progression of renal disease. Since a renal concentrating defect is an early functional abnormality in autosomal dominant polycystic kidney disease (ADPKD), defective medullary trapping and urinary excretion of ammonia may also occur early and have important pathophysiological consequences. The urinary pH and excretions of ammonia, titratable acid, and bicarbonate, were measured during a 24-hour baseline period and following the administration of ammonium chloride (100 mg/kg body wt) in ADPKD patients with normal glomerular filtration rate and in age- and gender-matched healthy control subjects. The distal nephron hydrogen ion secretory capacity was assessed during a bicarbonate infusion. Ammonia, sodium, pH, C3dg, and C5b-9 were measured in cyst fluid samples. The excretion rates of ammonia during the 24-hour baseline period and following the administration of ammonium chloride were significantly lower, and the relationship of ammonia excretion to urinary pH was significantly shifted downward in ADPKD. No difference in the increment of urinary pCO2 (delta pCO2) or the peripheral blood-urine pCO2 gradient (U-B pCO2) between ADPKD patients and control subjects was detected during a sodium bicarbonate infusion. Calculated concentrations of free-base ammonia in cyst fluid samples exceeded those calculated from reported concentrations of ammonia in renal venous blood of normal subjects. C3dg and C5b-9 were detected in some cyst fluids. The urinary excretion of ammonia is reduced in ADPKD patients with normal glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of the secretion of potassium by accompanying anions in humans.

In animals, secretion of potassium (K) in the cortical collecting duct (CCD) is modulated by the properties of the accompanying anion. In humans, results are inconclusive as previous studies have not differentiated between a kaliuresis due to a rise in the concentration of K from one due to an increase in the volume of urine. Our purpose was to study the effects of chloride (Cl) and bicarbonate on the secretion of K in the CCD in humans using the transtubular K concentration gradient (TTKG), a semi-quantitative index of secretion of K in the terminal CCD. After control blood and urine samples were obtained, all subjects ingested 0.2 mg fludrocortisone to ensure that mineralocorticoids were not limiting the secretion of K. The anionic composition of the urine was varied using three protocols: Normal subjects (N = 11) ingested cystine and methionine to induce sulfaturia; nine subjects with a contracted ECF volume (to lower the concentration of Cl in the urine) were also studied during sulfaturia following the ingestion of cystine and methionine; 13 normovolemic subjects were studied during bicarbonaturia following the ingestion of acetazolamide. When the concentration of Cl in the urine was greater than 15 mmol/liter, sulfate had no effect on the TTKG. With lower concentrations of Cl in the urine, the TTKG rose 1.5-fold. The TTKG rose 1.8-fold in the presence of bicarbonaturia despite concentrations of Cl in the urine that were greater than 15 mmol/liter, suggesting that bicarbonate has additional effects on this K secretory process. At comparable concentrations of sulfate and bicarbonate in the urine, the TTKG was increased only with bicarbonaturia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of parathyroid hormone on urinary acidification in the rat

To evaluate the effects of parathyroid hormone (PTH) on urinary acidification parameters, thyroparathyroidectomy was performed in normal (TPTX) and in calcium-supplemented rats (TPTX+Ca2**). Both groups were supplemented with thyroxin. Glomerular filtration rate (GFR) fell from 7.79 ñ 0.33 in the control group (C) to 4.88 ñ 0.26 ml min**-1Kg**-1 in TPTX, while net acid excretion fell from 5.65 ñ 0.22 in C to 3.76 ñ 0.26 µmol min**1Kg in TPTX. Kinetic dat of urinary acidification obtained by microperfusion techniques in proximal tubules showed that the half-time of acidification (t/2) rose from 4.75 ñ 0.24 s in C to 8.97 ñ 0.64s in TPTX and persisted elevated in TPTx +Ca**2+ (7.40 ñ 0.43s); in the latter group, stationary pH was not significantly different from that of the control group. Bicarbonate reabsorption (J**HCO3) fell from 2.18 ñ 0.15 in C to 0.823 ñ 0.082 in TPTX and was 1.53 ñ 0.073 nmol s**-1 cm**-2 in TPTX+Ca**2+. These suggest that normal pH gradients depend on normal calcium levels, but acidification half-times are dependent on PTH, which also contributes keeping glomerular hemodynamics and acidification rates at normal levels

Comparison of the effects of parathyroid hormone (PTH) and recombinant PTH-related protein on bicarbonate excretion by the isolated perfused rat kidney.

The isolated perfused rat kidney was used to study the effects of amino-terminal fragments of human parathyroid hormone, hPTH(1-34), bovine parathyroid hormone, bPTH(1-84) and of PTH-related proteins, PTHrP(1-34), PTHrP(1-84), PTHrP(1-108) and PTHrP(1-141) on urinary bicarbonate excretion. PTHrP(1-34) (7 nmol/l), bPTH(1-84) (5.5 nmol/l) and hPTH(1-34) (7 nmol/l) had similar effects in increasing bicarbonate excretion with respect to the control. At lower concentrations (0.7 nmol/l) all PTHrP components, but not hPTH(1-34) or bPTH(1-84) increased bicarbonate excretion significantly. Infusions of PTHrP(1-108) and PTHrP(1-141) at 0.7 nmol/l, while associated with a rise in urinary bicarbonate concentration and excretion during the early stages of perfusion, produced a sharp decline in bicarbonate concentration and excretion in the latter part of perfusion. The different peptides produced no significant differences in glomerular filtration rate, fractional excretion of sodium or urine volume. The absence of substantial differences between the effects of hPTH(1-34) and PTHrP(1-34) are as noted in previous studies. The differences between PTHrP(1-108)/PTHrP(1-141) and PTHrP(1-34) demonstrated here are consistent with (1) the clinical manifestations of acidosis in hyperparathyroidism and alkalosis in humoral hypercalcaemia of malignancy, and (2) an independent action of a component of PTHrP beyond amino acids 1-34.

Renal ammonia and bicarbonate production in chronic renal failure.

A characteristic feature of chronic renal failure (CRF) is decreased urinary NH4+ excretion and an alteration in systemic acid-base balance. In normal humans, glutamine is an important precursor of urinary NH4+; however, in CRF, renal glutamine extraction is significantly decreased. This finding suggests that alternate sources for urinary NH4+ exist. In addition to being an important precursor of urinary NH4+, the metabolism of glutamine generates alpha-ketoglutarate, an important substrate for new renal HCO3- generation in the proximal tubule. A useful model of the metabolic derangements in human CRF is the subtotally nephrectomized rat. In this review, the ammoniagenic pathways in this model of CRF are characterized with an emphasis on the role of glutathione and gamma-glutamyltransferase. In addition, recent data are presented on the production and partitioning of NH4+ and HCO3- into blood and urine in normal rats and rats with CRF.

Sodium and bicarbonate reabsorption in microperfused proximal tubules from the denervated rat kidney: relationship to cortical Na-K-ATPase activity.

Although numerous studies have documented the effects of the renal nerves on kidney function, the mechanisms involved in the diuresis have yet to be elucidated. The present study was undertaken to examine the effect of acute unilateral renal denervation (DNX) on proximal tubular absorption of fluid and bicarbonate and to determine if acute DNX was associated with changes in Na-K-ATPase activity. Acute DNX caused significant increases in urine flow and absolute and fractional excretions of Na, HCO3 and K compared to the contralateral control kidney (INN) or sham denervated kidneys in normal rats as well as in rats made alkalotic by the I.V. infusion of 150 mM NaHCO3. These effects were seen without significant changes in GFR. When proximal convoluted tubules (PCT) were perfused with bicarbonate-Ringer's solution DNX resulted in a 67% decrease in fluid reabsorption (INN: 3.0 +/- 0.2 vs DNX: 1.0 +/- 0.1 nl/min/mm; p less than 0.001) and a 40% decline in bicarbonate (total CO2) reabsorption (INN: 151.3 +/- 8.8 vs DNX: 94.5 +/- 10.1 pmol/min/mm; p less than 0.01). Acute DNX caused a significant reduction in Na-K-ATPase activity measured in microsomes derived from the outer cortex of the kidney (INN: 13.2 +/- 1.3 vs DNX: 10.9 +/- 0.7 mumol PO4/mg prot/hr; p less than 0.01) while Mg-ATPase was unaffected. Sham denervation had no effect on any of the above parameters. These results indicate that the renal nerves play an important role in the regulation of bicarbonate and fluid reabsorption in the PCT. The diuresis, natriuresis, and bicarbonaturia associated with acute unilateral renal denervation may be the direct result of inhibition of Na-K-ATPase activity.

Experimental Fanconi's syndrome resulting from 4-pentenoate infusion in the dog.

Studies were performed in anesthetized dogs to evaluate the effects of 4-pentenoate on urinary electrolyte excretion and renal metabolism. The intravenous administration of 4-pentenoate (1 mumol.kg-1.min-1 during 180 min) markedly increased the urinary excretion of bicarbonate, phosphate, potassium, amino acids, glucose, and various organic anions, whereas that of sodium and chloride also rose but less strikingly. These results suggest that 4-pentenoate markedly inhibits the proximal reabsorption of various solutes and therefore reproduces an experimental Fanconi's syndrome. Despite the rise in renal cortical concentration of alpha-ketoglutarate, glutamine utilization and total ammonia production expressed per 100 ml glomerular filtration rate increased following 4-pentenoate infusion, the ammonia being diverted into the renal vein. This increment in glutamine utilization was equal to the combined rise in the renal production of glutamate and alpha-ketoglutarate. By contrast, renal lactate utilization was drastically reduced. A causal relationship between the decreased renal cortical ATP concentration and the inhibited reabsorption of various solutes is suggested but cannot be established unequivocally.

Recent advances in the cellular mechanisms and hormonal regulation of urine acidification.

Excellent reviews dealing with the subject of tubular fluid and urine acidification have been published in recent years. This review focuses on the cellular mechanisms and hormonal regulation of H+/HCO3- transport by the renal tubule.

The stability of pH, PCO2, and calculated [HCO3] of urine samples collected under oil.

In order to determine the stability of directly measured pH and PCO2, and calculated [HCO3] in stored urine, 11 alkali-loaded normal subjects provided 33 spot and sixteen 24-hour mineral oil-covered, thymol-preserved, refrigerated urine samples. For the spot samples, pH and PCO2 were measured immediately and again at 4 and 24 h. In addition, immediately after voiding, 24 of the spot samples were split into oil-covered and no-oil moieties and analyzed immediately and again at 4 and 24 h. pH and PCO2 measurements of the 24-hour collections were carried out immediately after completion and again 24 h later. The results demonstrated the importance of using oil to limit the escape of CO2 from stored urine. Thus, after 24 h the oil-uncovered subgroup of 24 spot urine samples sustained a 82% decline in PCO2 and 20% fall in [HCO3]. In contrast, the corresponding percentage decrements in the oil-covered samples were 16 and 1%, respectively. The results also indicated that even with oil there is loss of CO2, which increases with time and which shows a statistically significant direct correlation with the baseline level of PCO2. Nevertheless, modest loss of CO2 usually produces only slight decrements in [HCO3] because of the countervailing influence of the resultant increase in pH. We conclude that the use of mineral oil is necessary in order to obtain adequate stability of PCO2, pH and [HCO3] in refrigerated urine requiring several hours or more of storage.

[The initial presentation of renal tubular syndrome]. / Die initiale Präsentation renal tubulärer Syndrome.

History, clinical presentation and first laboratory results were analyzed in three patients with cystinosis and in three patients with distal renal tubular acidosis. Growth failure, gastrointestinal tract disturbances, polydipsia, and polyuria were the most constant findings on history. Patients with distal renal tubular acidosis had a shorter period of clinical symptoms. All patients presented with dystrophy and dehydration. First laboratory investigation uniformly showed metabolic acidosis, high urinary-pH, and in spite of dehydration a low osmolarity of the first voided urine specimen. There were lower values of serum potassium and of urine osmolarity in cystinosis. In addition, metabolic acidosis was not so pronounced. Our study shows that history, clinical presentation and the results of a few simple laboratory investigations can indicate the presence of a renal tubular disorder even on admission of the patients.

Tubulopathy in nephrolithiasis: consequence rather than cause.

To address whether a renal tubular dysfunction is encountered in a particular patient subgroup with urolithiasis, the following parameters of tubular function were measured in urine taken in the morning from 214 stone formers after fasting: pH, excretion of lysozyme and gamma-glutamyl transferase (gamma-GT); fractional excretion (FE) of glucose, insulin, Mg, K, and HCO3 after an alkali loading; and the renal threshold for phosphate (TmP/GFR). The following diagnoses were made in the patient group: primary hyperparathyroidism (N = 8), medullary sponge kidneys (N = 21), hyperuricemia (N = 10), cystinuria (N = 2), struvite stone disease (N = 6), idiopathic hypercalciuria of the absorptive (N = 25), dietary (N = 69) or renal (N = 7) type, and normocalciuric idiopathic urolithiasis (N = 66). In 31% of the patients TmP/GFR was below 0.80 mmole/liter and in 13% of the patients, FE HCO3 after alkali loading was above normal. Urinary excretion of lysozyme and that of gamma-GT both were elevated in 17% of the patients. FE glucose, FE insulin, FE Mg, and FE K were elevated in 8, 9, 3, and 7% of the patients, respectively. This study demonstrates that a significant number of stone formers present with signs of renal tubular dysfunction, primarily involving the proximal tubule since apparent leaks of phosphate and of bicarbonate were most frequently encountered. The defects were not specific for a given etiologic group of patients; on the other hand, occurrence was related to the presence of large stones in the pyelocaliceal system at the time data were gathered. Taken together these data suggest that the tubulopathy in nephrolithiasis is the consequence rather than the cause of the stone.