Novel Algorithm for the Differential Diagnosis of Hyponatraemia in Anuric Patients Undergoing Maintenance Haemodialysis.

INTRODUCTION: Hyponatraemia is associated with increased mortality in patients undergoing maintenance haemodialysis. In anuric patients, hyponatraemia development depends on the water-sodium ratio in retained fluid within the interdialysis interval (IDI). OBJECTIVE: This study aimed to calculate the retained sodium-retained water ratio in patients on maintenance haemodialysis and make a differential diagnosis of hyponatraemia according to these data. METHODS: The amount of retained water was determined as body weight gain (ΔBW) within the IDI. Sodium retention was calculated using our formula: eRNa+ = ΔBW × (SNa+)t2 - total body water (TBW)t1 × ([SNa+]t1 - [SNa+]t2), where TBW represents the calculated volume of the total body water and (SNa+)t1 and (SNa+)t2 represent the sodium concentration at the beginning and at the end of the IDI, respectively. We performed 89 measurements in 32 anuric patients on maintenance haemodialysis. RESULTS: Hyponatraemia was detected in 13 measurements at the end of the IDI. The ΔBW had no statistically significant difference between normonatraemic and hyponatraemic patients. Hyponatraemic patients had significantly lower levels of retained sodium. The retained water--retained sodium ratio facilitated in differentiating dilution hyponatraemia, nutritional hyponatraemia, depletion hyponatraemia, and dilution hyponatraemia associated with sodium wasting or malnutrition. CONCLUSION: The composition of retained fluid during the IDI may be hypotonic, hypertonic, or isotonic in relation to the extracellular fluid. Most of the hyponatraemic patients had hypotonic fluid retained during the IDI because of dilution as well as gastrointestinal sodium loss and/or malnutrition.

Spironolactone-furosemide combination therapy and acid-base disorders in liver cirrhosis patients
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OBJECTIVE: Respiratory alkalosis (RA) and dilutional hyperchloremic acidosis (DHA) are the most common acid-base balance (ABB) disorders in patients with liver cirrhosis. The aims of this study were to clarify whether RA develops in relation to DHA via respiratory compensation of metabolic acidosis and whether spironolactone in combination with low-dose furosemide - diuretics known to ameliorate DHA - positively affects RA in liver cirrhosis patients. MATERIALS AND METHODS: 59 patients with advanced cirrhosis were divided into two groups. Group D consisted of individuals (urine sodium concentration (UNa+) > 20 mmol/L) who responded to combination therapy consisting of spironolactone and low-dose furosemide. The non-D group consisted of individuals (UNa+ ≤ 20 mmol/L) who either did not respond to the treatment or who were not administered it. In both groups, we examined serum and urine concentrations of electrolytes and ABB parameters, including SNa+-SCl- and SNa+/SCl- values. RESULTS: In group D, we found a statistically significant relationship between pCO2 and SHCO3-: r = 0.756 (p < 0.001) and between pCO2 and SNa+-SCl-: r = 0.522 (p = 0.001). Neither Salb nor the corrected anion gap were associated with changes in SHCO3- or pCO2 values. Although SHCO3- values were normal, abnormal pCO2 values were observed in one third of group D patients. Based on multivariable analysis, SHCO3- proved to be a statistically significant influencing factor on pCO2 values. CONCLUSION: DHA contributes to the development of RA in individuals with liver cirrhosis. Reducing DHA by means of effective diuretic therapy comprising spironolactone and furosemide has a beneficial effect on RA in such patients.

[Disorders of water and electrolyte metabolism and changes in acid-base balance in patients with ascitic liver cirrhosis]. / Poruchy vodního a elektrolytového metabolismu a zmeny acidobazické rovnováhy u pacientu s ascitickou cirhózou jater.

In patients with advanced cirrhosis with ascites disorders of water and electrolyte metabolism are often present and they are associated with changes in acid-base balance. These changes can be very complicated, their diagnosis and treatment difficult. Dilutional hyponatremia is the most common disorder. Hyponatremia in these patients is associated with increased morbidity and mortality before and after liver transplantation. Other common disorders include hyperchloremic acidosis, hypokalemia, metabolic alkalosis, lactic acidosis, respiratory alkalosis. If renal impairment occurs (for example hepatorenal syndrome), metabolic acidosis and retention of acid metabolites may develop. The pathogenesis of these conditions applies primarily hemodynamic changes. Activation of renin-angiotensin-aldosterone system and non-osmotic stimulation of antidiuretic hormone trigger serious changes in water and natrium-chloride metabolism. This activation is clinically expressed like oedema, ascites, hydrothorax, low to zero natrium concentration in urine and increased urinary osmolality, which is higher than serum osmolality. In practice, the evaluation can be significantly modified by the ongoing diuretic therapy. Closer monitoring of water and electrolyte metabolism together with acid-base balance in patients with ascitic liver cirrhosis is important, not only in terms of diagnosis but especially in terms of therapy.

[Clinical evaluation of acid-base status: Henderson-Hasselbalch, or Stewart-Fencl approach?] / Klinické hodnocení poruch acidobázické rovnováhy: Hendersonuv-Hasselbalchuv, nebo Stewartuv-Fencluv prístup?

Two approaches have been used in clinical evaluation the acid-base status: traditional (bicarbonate-centered) is based on the Henderson-Hasselbalch equation complemented by calculation of the anion gap, and more recent quantitative approach proposed by Stewart and Fencl. The latter method defines the three independent variables, which regulate pH. These include: the difference between the sum of charges carried by strong plasma cations and anions termed the strong ion difference - SID (decrease causes acidosis, and vice versa); the total concentration of the weak non-volatile acids [Atot] (inorganic phosphate and albumin, decrease causes alkalosis and vice versa), and pCO2. According to this approach, pH and bicarbonate are dependent variables. Their concentrations change if and only if one or more independent variables are altered.The main advantage of the Stewart-Fencl approach is the calculation of the concentration of plasma acids, which are not routinely measured. In the traditional approach, their presence is inferred from the anion gap. The correction of the value of anion gap according to the serum albumin level increases the specificity. This correction brings traditional approach closer to the Stewart-Fencl method that precisely calculates unmeasured strong anions by further adjustment of the corrected anion gap according to the serum phosphate, calcium and magnesium levels. The precise calculation of unmeasured anions is important in critically ill patients with the metabolic breakdown, where the traditional approach may overlook the presence of unmeasured anions. Consideration of the sodium-chloride difference draws the attention to acid-base disturbance caused by change of the strong ion difference.

[The difference and ratio between serum concentrations of natrium and chlorides in patients with hyponatremia]. / Diference a pomer sérových koncentrací natria a chloridu u pacientu s hyponatremií.

UNLABELLED: The differential diagnosis of hyponatremia is often difficult. This most frequently occurring disorder of the water and electrolyte metabolism is frequently connected with deviations relating to the acid-base balance (ABB). This survey analyzes the relationship between the changes of the volume of body fluids and ABB and infers to what extent the analysis of combinations of the two disorders can support the differential diagnosis of different forms of hyponatremia (differentiation between the dilution vs. depletion forms). The changes of the total water volume (CTV) and ABB may be presented at the same time in the values of the difference and ratio between serum concentrations of natrium and chlorides (SNa+ - SCl-; SNa+/SCl-). The changes of these quantities are analyzed in the models of pathologies connected through hyponatremia and ABB related deviations: (i) retention of solute-free water (hyponatremia associated with dilution acidosis); (ii) retention Na+ in combination with water retention (hyponatremia associated with dilution and hyperchloremic acidosis); (iii) depletion Na+ combined with water depletion (depletion hyponatremia combined with hypochloremic alkalosis), and (iv) combination of dilution and depletion (hyponatremia which may be associated with different ABB related deviations). This survey specifies the extent to which the applied models are consistent with the existing clinical findings and experience. The examinations SNa+ - SCl- and SNa+/SCl- rely only on routinely used laboratory test methods. Monitoring of these quantities may contribute to continuous assessment of the effect of a chosen therapy. KEY WORDS: acid-base balance - depletion hyponatremia - differential diagnosis of hyponatremia - dilution hyponatremia - hyponatremia - retention of solute-free water - body fluid volumes.

[Granulomatosis with polyangiitis manifested as diabetes insipidus]. / Granulomatóza s polyangiitidou manifestující se jako diabetes insipidus.

UNLABELLED: The case report shows a surprising presentation of pulmonary granulomatosis with polyangiitis (GPA) through symptoms of diabetes insipidus (DI) with granulomatous infiltration of the pituitary gland. The pituitary hormonal dysfunction as a result of granulomatosis of the pituitary gland is rare. Several studies have demonstrated that the incidence of the pituitary dysfunction reaches approx. 1 % of the patients with GPA. However it is mostly presented in patients with the disease already diagnosed. The patient described by us had no clinical expressions of GPA in the respiratory tract. He presented with polyuria and polydipsia. It was not until a more detailed examination of these symptoms was performed that a focal lung disease was detected and diagnosed as GPA. KEY WORDS: diabetes insipidus - granulomatosis with polyangiitis - granulomatous infiltration of the pituitary gland - pituitary hormonal dysfunction.

[Metabolic acidosis in chronic kidney disease]. / Metabolická acidóza u chronického onemocnení ledvin.

Metabolic acidosis (MAC) is a constant symptom of chronic kidney disease (CKD) in advanced stages. However, its onset and degree do not depend only on the decrease of glomerular filtration but also on tubular functions. Therefore, in patients with predominant tubulointerstitial involvement it may already appear in earlier stages of CKD, usually as MAC with normal anion gap. The progressive decrease of glomerular filtration leads to acid retention that develops in a MAC with an increased anion gap. MAC has many adverse clinical impacts, including the progression of the underlying CKD. The development and degree of MAC in CKD is usually influenced by a combination of several pathophysiological mechanisms and a number of external factors, the most important of them being the diet - the intake and type of proteins - and hydration status. A correct identification of the factors contributing to MAC determines the therapeutic possibilities of its correction. However, optimal serum concentrations of bicarbonate in conservatively treated patients are still subject to debate. Opinions are even more divided on the question of optimal serum concentration of bicarbonate before and after dialysis, in particular due to the risk of post-dialysis meta-bolic alkalosis.Key words: dialysate bicarbonate - chronic kidney disease - metabolic acidosis - sodium bicarbonate - sodium-chloride difference.

[Present possibilities of monitoring the effectiveness of hyponatremia therapy]. / Soucasné moznosti sledování efektivnosti terapie hyponatremie.

Changes to the overall volume of body water and acid base equilibrium can be reflected in the values of differences and ratios relating to serum concentrations of natrium and chlorides. Both these quantities can be used for patients with hyponatremia in the hyponatremia differential diagnosis. This paper presents a case study which is an example of the clinical use of differences in and ratios of serum concentrations of natrium and chlorides when monitoring effectiveness of the therapy.Key words: acid base equilibrium - depletion hyponatremia - differential diagnosis of hyponatremia - dilution hyponatremia.

[Serum concentration and tubular resorption of sodium and chloride in patients with chronic renal disease]. / Sérové koncentrace sodíku a chloridu a tubulární resorpce techto iontu u pacientu s chronickým renálním onemocnením.

Tubular transport of sodium (TNa+) and chloride (TCl-) is decreased in patients with chronic kidney disease. The decrease of TCl- is relatively lower than that of TNa+. These changes of tubular transport of Na+ and Cl- participate on the development of acid base disturbance in patients with chronic kidney disease and with their glomerular filtration rate lower than 0.5 ml/s/1.73 m2.

Acid-base disorders associated with serum electrolyte patterns in patients on hemodiafiltration.

BACKGROUND: Metabolic acidosis (MAC) is a common aspect of dialysis-dependent patients. It is definitely caused by acid retention; however, the influence of other plasma ions is unclear. Understanding the mechanism of MAC and its correction is important when choosing the dialysis solution. Therefore, we assessed the relationship between intradialytic change of acid-base status and serum electrolytes. METHODS: We studied 68 patients on post-dilution hemodiafiltration, using dialysate bicarbonate concentration 32mmol/L. The acid-base disorders were evaluated by the traditional Siggaard-Anderson and modern Stewart approaches. RESULTS: The mean pre-dialysis pH was 7.38, standard base excess (SBE) -1.5, undetermined anions (UA(-)) 7.5, sodium-chloride difference (Diff(NaCl)) 36.2mmol/L. MAC was present in 34% of patients, of which 83% had an increased UA(-) as a major cause of MAC. The mean nPCR was 0.99g/kg/day and correlated negatively with SBE. After dialysis, metabolic alkalosis predominated in 81%. The mean post-dialysis pH was 7.45, SBE 4, UA(-) 2.6, Diff(NaCl) 36.9mmol/L. ΔSBE significantly correlated with ΔUA(-), but not with ΔDiff(NaCl) or ΔCl(-). CONCLUSIONS: MAC in patients on hemodiafiltration is mainly caused by acid retention and is associated with higher protein intake. We did not prove the effect of sodium or chloride on acid-base balance. Even though we used a relatively low concentration of dialysate bicarbonate, we recorded a high proportion of post-dialysis alkalosis caused by the excessive decrease of undetermined anions, which had been completely replaced by bicarbonate and indicated the elimination of undesirable anions, as well as of normal endogenous anions.

[Investigation of tubular reabsorption of phosphates in patients with chronic kidney disease]. / Vysetrování tubulární resorpce fosfátu u pacientu s chronickým onemocnením ledvin.

INTRODUCTION: Moderate to medium decrease in glomerular filtration (GFR) in individuals with chronic kidney disease (CKD) does not need to be associated with hyperphosphatemia due to an adaptive decrease in tubular reabsorption of phosphates (TRPi) in residual nephrons. The clinical assessment of this function is performed based on the measurement of fractional phosphate excretion (FEPi), which is a quantity specifying the proportion of the filtered amount of phosphates which is excreted in the urine. This quantity may provide useful information about the involvement of kidneys in phosphate homeostasis of the internal environment. This study focuses on the comparison of a kr(FEPi) value examined based on a ratio of a phosphate clearance (CPi) and a creatinine clearance (CKr) marked kr(FEPi), and a value calculated based on a ratio of CPi and an exactly measured GFR as an inulin clearance (Cin), marked as in(FEPi).The goal of comparing the two methods of examining FEPi was to establish to what extent it is possible to evaluate the degree of inhibition of tubular phosphate transport in residual nephrons based on a simple examination of kr(FEPi) . METHODOLOGY: The examination of in(FEPi) and kr(FEPi) was carried out for 53 patients with CKD. The values of the examined quantities were as follows: SKr 199±45 µmol/l; SPi 1.41±0.29 mmol/l; CKr 0,95±0.36 ml/s/1.73 m2; Cin 0.71±0.25 ml/s/1.73 m2. For the purpose of comparison a cohort of 18 healthy volunteers was examined. RESULTS: For individuals with CKD an average value of kr(FEPi) equalled 29.1±10.9% and in(FEPi) 52.4±4.3%. The values of in(FEPi) were higher than kr(FEPi) (p<0.001) for all patients, although an average CPi value for patients with CKD did not significantly differ from the control cohort (0.22 vs 0.21 ml/s/1.73 m2). The values of in(FEPi) increased proportionally to SKr values and at higher values SKr (>300 µmol/l) they gradually approached 100% (indicating the complete inhibition of tubular reabsorption of phosphates in residual nephrons). The values of in(FEPi) were higher in all patients with CKD than kr(FEPi) as expected, likely because the value CKr decreases at a slower rate than Cin (GFR) in individuals with CKD as a result of increased tubular secretion of creatinine in residual nephrons. CONCLUSION: The results of this study support the assumption that, provided the values of kr(FEPi) which are easily measurable in clinical practice have reached 50-60%, almost complete inhibition of tubular reabsorption of phosphates in residual nephrons must be assumed and no favourable effect of phosphatonins on renal phosphate excretion can be expected. When looking for new possibilities of inhibition of tubular phosphate reabsorption, potential adverse effects of phosphatonins on organs must be considered.

The relationship between estimated GFR based on the CKD-EPI formula and renal inulin clearance in potential kidney donors.

It is not yet clear whether or not renal function in the living donor can be sufficiently assessed by estimated glomerular filtration rate (GFR) using creatinine-based equations. The present paper investigates the relationship between GFR values determined using renal inulin clearance (Cin) and those estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Our study was performed in 287 potential kidney donors with a mean age of 48 ± 10 years. Mean Cin was 1.47 ± 0.28 (1.10 - 2.50) mL/s/1.73 m2. Total bias when using the CKDEPI formula was -0.0183 mL/s/1.73 m2, precision 0.263 mL/s/1.73 m2, and accuracy 90.6% within ± 30% of Cin. The sensitivity of CKD-EPI to estimate a decrease in Cin below 1.33 mL/s/1.73 m2 was 50.5%, with an 85% specificity of detecting a value above the cutoff. Receiver-operating curve analysis for the above produced an area under the curve of 0.766 ± 0.0285 (CI 0.712 - 0.813). For donor screening purposes, CKD-EPI should be interpreted with great caution.

Effects of high-tone external muscle stimulation on renal function in healthy volunteers.

OBJECTIVE AND DESIGN: Hightone external muscle stimulation (HTEMS) ameliorates pain and discomfort of patients with polyneuropathy. Since some patients reported about an urge to urinate during these treatments, the potential effects of HTEMS application on renal function were investigated. For this purpose in healthy subjects, we analyzed in the current study the acute effects of electrotherapy on parameters of renal function. INTERVENTIONS: 24 healthy volunteers (14 women and 10 men), mean age 26 ± 4 years, were enrolled. The protocol was composed of a run-in period, a pre-treatment period, the active HTEMS treatment period of both lower extremities and the post-treatment period. The duration of each period was 60 min. Urine collection and blood samples were taken at the beginning and end of each period. To achieve a sufficient diuresis, the fluid intake was adapted to the amount of diuresis. Parameters of renal function included diuresis, glomerular filtration rate (endogenous creatinine clearance) and absolute and fractional sodium excretion. Moreover blood pressure and heart rate were monitored. RESULTS: HTEMS led to a significant increase of creatinine clearance and fractional sodium excretion which was limited to the active treatment period. CONCLUSION: These findings show for the first time that HTEMS can transiently increase glomerular filtration rate associated with a decreased tubular sodium reabsorption. The underlying mechanisms are to be elucidated.

The clinician and estimation of glomerular filtration rate by creatinine-based formulas: current limitations and quo vadis.

The GFR has a paramount diagnostic and staging role in the Kidney Disease Outcome Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease (K/DOQI-CKD). The most widely used serum creatinine-based formulas in adults for estimated GFR (eGFR) are the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease Study (MDRD). Recently, a new Chronic Kidney Disease Epidemiology Collaboration equation has been developed. Review of the literature revealed that CG and MDRD formulas correctly assigned overall only 64% and 62%, respectively, of the subjects to their actual K/DOQI-CKD classification's GFR groups as determined by measured GFR (mGFR). This suggests that approximately 10 million (38%) subjects may have been misclassified on the basis of estimated CKD prevalence of 26.3 million adults in the United States. The purpose of this review is to help the clinician understand the limitations of using eGFR in daily practice. We also elaborate upon issues such as the differences among markers of mGFR, the validity of adjusting GFR for body surface area in certain populations, the limited data on boundaries for normal mGFR according to age, gender, and race, the need for calibration of a wide spectrum of serum creatinine measurements, the lack of actual eGFR value above 60 ml/min per 1.73 m(2) and reference for normal mGFR in the clinical laboratories' reports, and the performance evaluation of the eGFR formulas. Several pitfalls have to be overcome before we can reliably determine health and disease in daily nephrology practice to preserve the first rule of practicing medicine: primum non nocere.

Acid-base balance in peritoneal dialysis patients: a Stewart-Fencl analysis.

BACKGROUND: Evaluation of acid-base disorders using the Stewart-Fencl principle is based on assessment of independent factors: strong ion difference (SID) and the total concentration of non-volatile weak acids (Atot). This approach allows for a more detailed evaluation of the cause of acid-base imbalance than the conventional bicarbonate-centered approach based on the Henderson-Hasselbalch principle, which is a necessary yet insufficient condition to describe the state of the system. The aim of our study was to assess acid-base disorders in peritoneal dialysis (PD) patients using both of these principles. METHODS: A total of 17 patients with chronic renal failure (10 men), aged 60.7 (22-84) years, treated by PD for 25.7 (1-147) months were examined. A control group included 17 healthy volunteers (HV) (8 males), with a mean age of 42.7 (22-77) years and normal renal function. Patients were treated with a solution containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) as buffers; eleven of them used, during the nighttime dwell, a solution with icodextrin buffered by lactate at a concentration of 40 mmol/L. The following equations were employed for calculations of acid-base parameters according to the Stewart-Fencl principle. The first is SID = [Na+] + [K+] + 2[Ca(2+)] + 2[Mg(2+)] - [Cl-] - [UA-], where SID is the strong ion difference and [UA-] is the concentration of undetermined anions. For practical calculation of SID, the second equation, SID = [HCO3-] + [Alb-] + [Pi-], was used, where [Alb-] and [Pi-] are the charges carried by albumin and phosphates. The third is Atot, the total concentration of weak non-volatile acids, albumin [Alb] and phosphates [Pi]. RESULTS: The capillary blood pH in PD group was 7.41 (7.27-7.48), [HCO3-] levels 23.7 (17.6-29.5) mmol/L, SID 36.3 (29.5-41.3) mmol/L, sodium-chloride difference 39.0 (31.0-44.0) mmol/L, [Pi] 1.60 (0.83-2.54) mmol/L, and [Alb] 39.7 (28.8-43.4) g/L (median, min-max). Bicarbonate in blood correlated positively with SID (Rho = 0.823; p < 0.001), with the sodium-chloride difference (Rho = 0.649; p < 0.01) and pH (Rho = 0.754; p < 0.001), and negatively with residual renal function (Rho = -0.517; p < 0.05). Moreover, the sodium-chloride difference was also found to correlate with SID (Rho = 0.653; p < 0.01). While the groups of PD and HV patients did not differ in median bicarbonate levels, significantly lower median value of SID were observed in PD patients, 36.3 vs. 39.3 mmol/L (p < 0.01); additionally, PD patients were shown to have significantly lower mean value of serum sodium levels, 138 vs. 141 mmol/L (p < 0.01), and serum chlorides levels, 100 vs. 104 mmol/L (p < 0.001). Despite the higher [UA-] levels in PD patients, 9.1 vs. 5.4 mmol/L (p < 0.001), this parameter was not found to correlate with bicarbonate levels. CONCLUSIONS: The results suggest that the decreased bicarbonate in PD patients results from a combination of decreased sodium-chloride difference and mildly increased unmeasured anions.