Karel Matousovic

Urinary transforming growth factor-β1 in children with obstructive uropathy.

Aim:  Obstructive uropathies (OU) in childhood constitute one of the major causes of chronic renal insufficiency. Transforming growth factor‐β1 (TGF‐β1) is considered to be the major fibrogenic growth factor. The aim of the present study was to investigate urinary TGF‐β1 levels in children with obstructive and non‐obstructive uropathies (NOU).

Effect of donor/recipient body weight ratio, donor weight, recipient weight and donor age on kidney graft function in children

BACKGROUND We hypothesized that supplementing a higher mass of renal parenchyma from adult donors, and their younger age, would improve graft function in paediatric recipients. METHODS We calculated estimated glomerular filtration rate (eGFR; Schwartz formula) and absolute glomerular filtration rate (absGFR) in 57 renal-grafted children (1995-2007) aged 3.1-17.9 years, weighing 12.9-85.0 kg, on discharge from the hospital after transplantation (TPL), 1 year after TPL and at the last follow-up (1.5-11.7 years after TPL). We correlated their eGFR with the individual ratio between the donor and the recipient body weight at the time of TPL (donor/recipient body weight ratio; D/R BWR), and we evaluated the effect of the donor and the actual recipient body weight on the eGFR and absGFR. RESULTS The D/R BWR varied from 0.65 to 5.23. We found a significant positive correlation between D/R BWR and eGFR at discharge from the hospital (P < 0.001), 1-year post-TPL (P < 0.001) and at the last follow-up (P < 0.05). Using multiple linear regression analyses, we found that both eGFR and absGFR values were much more determined by the actual recipient weight than by the donor weight (27/6% and 43/4% at discharge, by 24/4% and 57/0% 1 year after TPL, and 0/0% and 20/0% at the end of the follow-up). A tendency for lower eGFR with increasing age of donors was apparent at discharge and 1 year after TPL, but it reached statistical significance only at the last follow-up (r = 0.4254, P < 0.01). CONCLUSION In paediatric renal transplants, the value of D/R BWR directly correlated with eGFR in the early and late posttransplant periods. However, this correlation was mainly influenced by the recipient weight, while the donor weight played only a minor or negligible role.

Malignant Wegener's granulomatosis with fibrosing mediastinitis and vena cava superior syndrome.

A 47-year-old man was admitted to hospital for migratory joint pain, fatigue, and cough with bloody sputum and proteinuria with increased serum creatinine level. Diagnosis of Wegener’s granulomatosis was established. During follow-up, the vena cava superior syndrome developed. The patient died of respiratory failure after 12 years of follow-up. The autopsy revealed rigid, whitish, 12 mm thick tissue, which embedded and compressed the large vessels upwards from their origin in the heart, thus causing vena cava superior syndrome. This tissue was composed of fibrous material without inflammatory cellulization. We consider this fibrous tissue as a manifestation of fibrosing mediastinitis that may or may not share pathogenesis with Wegener’s granulomatosis.

Sodium-Chloride Difference as a Simple Parameter for Acid-Base Status Assessment

To the Editor: We read with great interest the recent article by Adrogué and Madias and agree with all its conclusions. However, the article did not comment on a simple and useful parameter for assessing acid-base status; namely, the difference between 2 major serum ions, sodium and chloride. The relationship between serum bicarbonate, sodium-chloride difference, and the anion gap (AG) can be expressed by the equation: AG 5 Na 2 Cl 2 HCO3 ; modified to HCO3 5 (Na 2 Cl) – AG. It implies that if sodium-chloride difference remains constant, there is an inverse linear relationship between bicarbonate and the AG. If the AG is unchanged, a relationship must exist between bicarbonate and sodium-chloride difference. Therefore, a decrease in sodium-chloride difference is associated with bicarbonate loss or dilution acidosis. Serum sodium and

A “Lingering Mystery” of Postdialysis Serum Bicarbonate Concentration

References 1. Riccio E, Sabbatini M, Esposito G, Pisani A. Catheter-based renal denervation in ADPKD: just for pain control? Am J Kidney Dis. 2014;64(6):999. 2. Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373(9671):1275-1281. 3. Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 trial): a randomised controlled trial. Lancet. 2010;376(9756):1903-1909. 4. Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393-1401. 5. Harrison JL, Hildreth CM, Callahan SM, Goodchild AK, Phillips JK. Cardiovascular autonomic dysfunction in a novel rodent model of polycystic kidney disease. Auton Neurosci. 2010;152(1-2):60-66. 6. Klein IH, Ligtenberg G, Oey PL, Koomans HA, Blankestijn PJ. Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension. J Am Soc Nephrol. 2001;12(11):2427-2433. 7. Shetty SV, Roberts TJ, Schlaich MP. Percutaneous transluminal renal denervation: a potential treatment option for polycystic kidney disease-related pain? Int J Cardiol. 2013;162(3): e58-e59. 8. Prejbisz A, Kadziela J, Lewandowski J, et al. Effect of percutaneous renal denervation on blood pressure level and sympathetic activity in a patient with polycystic kidney disease. Clin Res Cardiol. 2014;103(3):251-253. 9. Walsh N, Sarria JE. Management of chronic pain in a patient with autosomal dominant polycystic kidney disease by sequential celiac plexus blockade, radiofrequency ablation, and spinal cord stimulation. Am J Kidney Dis. 2012;59(6): 858-861. 10. Riccio E, Esposito G, Franzone A, Imbriaco M, Santangelo M, Pisani A. Renal sympathetic-nerve ablation for uncontrolled hypertension in a patient with single-kidney autosomal dominant polycystic kidney disease. J Clin Hypertens (Greenwich). 2014;16(5):385-386.

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[Ca2+] + 2[Mg2+] − [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.

The use of sodium-chloride difference and chloride-sodium ratio in the evaluation of metabolic acidosis in critically ill patients

Sir, We read the study of Kurt et al. [4] and we believe that sodium–chloride difference (Diff(NaCl)) and Cl-Na ratio cannot be considered as an alternative method for assessment of unmeasured anions or tissue acids (TA). Significant correlation between Cl-Na ratio and TA is not an unexpected result because metabolic acidosis (MAC) is generally caused either by loss of bicarbonate (insufficient renal synthesis of HCO3 compensated by an increase of Cl ) or by retention of acids (chlorides remain unchanged), frequently by both. The correlation is a weak evidence that one method can replace another. The confidence interval is not specified but at first glance it is apparent that variability is too high (Fig. 1e). Cl-Na ratio cannot be reliably used as a bedside method as it cannot exclude the accumulation of TA in individual case. Cl-Na ratio indicates only approximately whether MAC with unchanged Cl is associated with retention of acids and MAC with hyperchloremia with insufficient synthesis of bicarbonate. Therefore, this examination must always be complemented by AG(corr) which is an adequate alternative to TA [1, 2]. In the study, we miss a control group and normal values of Na, Cl, Cl-Na ratio and Diff(NaCl) related to age and its variance. Therefore, the incidence of hypochloremic MAC cannot be evaluated. We support the use of Diff(NaCl) for detection of disturbances in sodium chloride metabolism, even if the isolated concentrations of Na and Cl are still within normal limits [3]. We believe that Cl-Na ratio adds supplementary data to levels of Diff(NaCl) in its pathological range (otherwise the Cl-Na ratio is also within normal limits) as it may clarify whether the change in Diff(NaCl) is mainly due to dilution/contraction or due to primary ion imbalance. Theoretically, the Cl-Na ratio remains unchanged in case of pure dilution/contraction whereas Diff(NaCl) decreases with dilution and increases with contraction.

Contribution of Jan Brod to Nephrology

Jan Brod (1912–1985), Professor of Medicine of Charles University, Prague, was one of the outstanding personalities of the Czechoslovak medicine and European nephrology of the 20th century. He was an eminent clinician, teacher and scientist who belonged among the founders of renal medicine in Europe. He grew up in the scientific tradition of Prague and Vienna and he was trained by some outstanding personalities, particularly Paul Wood. He became famous due to his pathophysiological-clinical approach to hypertension, heart and kidney diseases. He was not only interested in renal and cardiac physiology but in the entire clinical nephrology. He was among the first clinicians who started to use creatinine clearance in routine practice. His early work was also performed in the field of acute glomerulonephritis and in interstitial nephritis. Later he was interested in water and electrolytes in heart failure and the pathogenesis of edema, and he published priority data on the hemodynamic pattern in emotional stress. Furthermore, it is for sure that he was one of the first cardionephrologists, too. As early as in 1950, he studied diurnal variation in renal perfusion and urinary output in heart failure and later the effect of the adrenergic blockade on the renal hemodynamics in heart failure. Up to his exile in 1968, he served as the head of the Institute for Cardiovascular Research based in Prague and later on, up to his retirement, as the head of the Department of Nephrology in Hannover. He was a founding member of the International Society of Nephrology and president of its 2nd congress held in Prague in 1963. Throughout his life, Jan Brod remained a political man who voiced his opinions. Despite two exiles, he was always the Czech patriot. He holds a special place in the history of Czechoslovak and European nephrology.

Importance of serum [Na+] and [Cl-] difference in acid-base status classification.

To the Editor Nguyen et al. concluded that the results of the Stewart-Fencl approach to the interpretation of acidbase status vary according to the analyzer used. This approach requires a number of analytical methods and can cumulate measurement errors. It is uncertain whether this challenging approach offers more information than the traditional one introduced by Henderson-Hasselbalch combined with anion gap corrected for serum albumin concentration (AGcorr).* We would like to draw attention to the importance of [Na -Cl ] difference compared with [Na ] and [Cl ] evaluated separately. The authors emphasized that [Na ] and [Cl ] are the most important variables in the calculation of the apparent strong anion difference (SIDapp), but they did not evaluate [Na -Cl ] difference as a separate variable. Findings by Story et al. and our group indicate that this difference (lower limit 33 mmol/L in our laboratory) may decrease even if [Na ] and [Cl ] are within the normal range, because serum concentrations of these ions oscillate within a wide range of 10 mmol/L each. Therefore, we propose that the variables of the traditional approach should be replaced by [Na -Cl ] difference to detect the disturbance of acid-base status not caused by the retention of undetermined anions.