Jovanović O

Medium- and Long-Term Prognosis of Patients with Acute Poststreptococcal Glomerulonephritis

The prognosis of acute poststreptococcal glomerulonephritis (APSGN) is still a matter of considerable debate. In an attempt to elucidate this controversy, the medium-term prognosis was evaluated in 40 patients 5-9 years after the onset of the disease, and the long-term prognosis in 88 patients 10-17 years after the onset of the disease. All were sporadic cases. In the medium-term follow-up study, abnormalities were revealed in 5.0% (2/40) of the patients. Hypertension and proteinuria were the only abnormalities detected. In the long-term follow-up study, abnormalities were revealed in 6.8% (6/88) of the patients. Hypertension was found in 3.4, proteinuria in 2.3, and microhaematuria in 2.3% of the patients. In both studies, all patients had normal creatinine clearance. We conclude that the medium- and long-term outcome of patients with APSGN is excellent.

Interleukin-12 and interferon-γ production in childhood idiopathic nephrotic syndrome

Abstract. Cellular immune disturbances, and T lymphocyte function in particular, have been previously implicated in idiopathic nephrotic syndrome (INS) of childhood. There are different patterns of cytokine expression in various forms of glomerulonephritis, which suggests that local production of these peptides plays an important role in the pathogenesis and progression of glomerulonephritis. To investigate T-cell and monocyte/macrophage cytokine production in INS, interleukin-12 (IL-12) and interferon-γ (IFN-γ) production by peripheral blood mononuclear cells (PBMC) of 11 children with steroid-sensitive nephrotic syndrome (SSNS), 9 with focal segmental glomerulosclerosis (FSGS), and 17 healthy controls was determined. Children with SSNS were studied in relapse, during corticosteroid treatment, and in stable remission, off corticosteroid treatment. IL-12 was not detected in serum, urine, and in supernatants of unstimulated PBMC. IL-12 production by concanavalin A (Con A)-stimulated PBMC of children with SSNS and FSGS was not different from controls. IFN-γ production by Con A-stimulated PBMC was decreased in children with relapsing SSNS, both in relapse and and during corticosteroid treatment. However, in stable remission it was similar to controls. Markedly decreased IFN-γ production (P<0.001) was observed by pokeweed mitogen-stimulated PBMC of relapsing SSNS patients and moderately decreased production by PBMC of FSGS patients. This study has established a decreased production of IFN-γ by PBMC of relapsing SSNS and FSGS patients, but does not allow differentiation between these two different conditions. IL-12 did not have a pathogenic role in either SSNS or FSGS.

Clinical characteristics of haemorrhagic fever with renal syndrome in children

From January 1988 to September 1989, seven patients (4 girls and 3 boys, aged 3–12 years) with haemorrhagic fever with renal syndrome (HFRS) were hospitalised at the University Childrens Hospital in Belgrade. In four patients the disease appeared as a family outbreak, the others were sporadic cases. In six patients the clinical presentation was suggestive of HFRS, as they had fever with headache, myalgia, sore throat and gastrointestinal illness followed by renal abnormalities. However, severe haemorrhagic syndrome with petechia, haematoma, haematemesis and melaena was present in one patient only. Renal disease presented as nephritic syndrome and/or acute renal failure. Five patients recovered after 2–3 weeks without sequellae, one patient had decreased renal function 17 months after the start of the disease and the remaining patient died. In six patients the diagnosis of HFRS was confirmed serologically by a significant rise in antibody titres against hantaviruses, while in the patient with the fatal and fulminant course of the disease, the diagnosis was established on the basis of epidemiological and autopsy findings. We suggest that children living in endemic areas who develop an ill-defined, febrile and gastrointestinal disease with renal dysfunction should be evaluated for HFRS.

Effect of Dialysis Dose on Nutritional Status of Children on Chronic Hemodialysis

It had been suggested that larger hemodialysis (HD) doses in children could result in better appetite, higher protein intake, better nutritional status and better growth. We investigated how different HD doses affect protein intake and nutritional status of children on chronic HD. Indices of nutritional status used were normalized protein catabolic rate (nPCR) calculated by formal 3-sample urea kinetic modeling and serum albumin level. Data of 38 HD sessions in 15 stable patients (6 males, 9 females) aged 14.5 ± 3.28 years (mean ± SD) were analyzed. HD sessions were divided into three groups based on delivered Kt/V: group 1 (n = 5), inadequate (Kt/V < 1.3, mean 1.05 ± 0.14); group 2 (n = 12), adequate (Kt/V = 1.3–1.6, mean 1.50 ± 0.07) and group 3 (n = 21), high (Kt/V >1.6, mean 1.94 ± 0.22). Mean nPCR and Kt/V per patient during the studied week were estimated for 11 patients in whom 3 HD sessions were available within the 38 sessions analyzed. Serum albumin level was adequate in all patients (43.77 ± 2.28 g/l). Mean overall Kt/V and nPCR were 1.68 ± 0.36 and 1.26 ± 0.23, respectively, r = 0.430. Average nPCR differed between groups depending on Kt/V. It was lowest in group 1 (1.01 ± 0.12 g/kg/day) where the highest correlation between nPCR and Kt/V was found (r = 0.648). nPCR was higher and similar in groups 2 (1.27 ± 0.23 g/kg/day) and 3 (1.31 ± 0.22 g/kg/day), with low correlation coefficients between nPCR and Kt/V in both groups (r = 0.275 and r = 0.197, respectively). A weak positive correlation (r = 0.249) between nPCR and Kt/V was found when average weekly values per patient (n = 11) were analyzed. Results of groups 1 and 2 confirm, what is already well established in adults, that adequate dialysis needs to be achieved in order to insure good protein intake. However, our data clearly show that nPCR did not increase with a further increase in delivered HD dose, i.e. Kt/V >1.6. Our results show that the nutritional status of children on chronic HD does not seem to benefit from very high HD doses (Kt/V >1.6).

Hyponatremic hypertensive syndrome

Abstract We report on a 4-year-old girl with hyponatremic-hypertensive syndrome (HHS), a rare entity in childhood. The girl was referred to us from a local hospital with a history of recurrent fever, vomiting, and seizures. On admission she was markedly dehydrated. Initial investigations revealed severe hyponatremia (serum Na 120 mmol/l), hypochloremia (serum Cl 68 mmol/l), and mild hypokalemia (serum K 3.3 mmol/l), while serum calcium and magnesium were normal. Serum urea was 5 mmol/l and serum creatinine was 62 µmol/l. Despite hyponatremic dehydration, her urine output was high (2050 ml/24 h), as was her urinary sodium (168 mmol/24 h). She had massive transient proteinuria (maximal 1642 mg/24 h) while being severely hypertensive (blood pressure 210/160 mmHg). Further investigations revealed right kidney scarring, hyper-reflexive bladder dysfunction, massive brain infarcts, and myocardial left ventricular hypertrophy. Renal arteries were normal on arteriography. Blood pressure control resulted in normalization of serum and urinary electrolytes and decrease of proteinuria. Hyponatremia and transient massive proteinuria in this patient seem to be caused by high-pressure-forced diuresis due to malignant renoparenchymal hypertension.

Comparison of two methods for predicting equilibrated Kt/V (eKt/V) using true eKt/V value

Abstract Two methods have been suggested by Daugirdas and Schneditz (the rate equation), and Smye for predicting true equilibrated Kt/V (eKt/V) without the need for obtaining a blood sample 60 min after hemodialysis (HD). We compared the accuracy of these two methods when applied to pediatric HD. Thirty-eight standard pediatric HD sessions in 15 patients, (6 male, 9 female), aged 14.5±3.3 years, were analyzed. Kt/V was calculated by formal variable-volume single-pool urea kinetic model with post-HD urea taken at the end of HD (single-pool Kt/V), and with equilibrated urea (Ceq) taken 60 min after the end of HD (eKt/V). eKt/V was predicted by the rate equation from single-pool Kt/V and by the Smye method from predicted Ceq. Mean values obtained by both the rate equation (1.44±0.32, P>0.05) and by the Smye method (1.47±0.36, P>0.05) were similar to eKt/V (1.42±0.30), but correlation between results from the rate equation and eKt/V (r=0.863) was higher than between those from the Smye method and eKt/V (r=0.654). Average absolute error of the rate equation in predicting eKt/V was 0.118±0.114 (median 0.095) Kt/V units and 8.53%±8.36% (median 6.29%), while for the Smye method it was significantly higher [0.221±0.180 (median 0.190) Kt/V units, P=0.001; 16.49%±15.98% (median 11.88%) P=0.004]. High correlation between eKt/V and results from the rate equation indicates that urea rebound (expressed as ΔKt/V) is a function of the rate of dialysis (K/V). To test this, we analyzed the relationship of K/V and other parameters (session duration, body mass index, ultrafiltration rate, blood flow, and urea distribution volume) with ΔKt/V. The only significant (P<0.01) and highest correlation (r=0.442) was found for K/V. We conclude that in children on chronic HD, the rate equation is a better predictor of eKt/V than the Smye method, and that HD efficiency is the strongest determinant of postdialysis urea rebound in children.

Progressive tubulointerstitial nephritis and chronic cholestatic liver disease

We report the clinical and morphological features of a distinctive hepatorenal disorder in four patients and review the five similar patients in the literature. The main clinical characteristics were early onset of cholestatic liver disease and progressive tubulointerstitial nephritis leading to renal death in early childhood. Liver histology showed disturbed architecture with nodular and acinar formations and portal fibrosis and bile duct proliferation. Histological abnormalities in the kidney were severe interstitial fibrosis and tubular atrophy and dilatation, while the typical features of nephronophthisis were lacking. These clinical and morphological characteristics distinguish our patients from the majority described, as having nephronophthisis and congenital hepatic fibrosis or any other known syndrome with concomitant hepatorenel involvement. We suggest that the association of cholestatic liver disease and progressive tubulointerstitial nephritis represents a new syndrome.

Prediction of equilibrated urea in children on chronic hemodialysis.

Urea rebound (UR) after hemodialysis (HD) requires the use of equilibrated urea (Ceq) instead of immediate end-dialysis urea (Ct) for correct quantification of HD, which is impractical. A new formula for predicting Ceq in children is suggested in our study. Thirty eight standard pediatric HD sessions (single pool Kt/V = 1.70 +/- 0.35, K = 4.65 +/- 1.14 ml/min/kg, UF coeff. = 3.2-6.2 ml/h/mm Hg, t = 3.80 +/- 0.46 h) in 15 children (M: 6, F: 9), ages 14.5 +/- 3.28 years were analyzed. Blood samples were taken: before, 70 min from the start, at the end, and 60 min after the end of HD sessions. After correlating UR (20.32 +/- 7.74%) to various HD parameters, we found that it was mainly determined by HD efficiency parameters. Therefore we correlated Ceq to HD efficiency parameters (Ct, urea reduction ratio, Kt/V, and K/V) and found a very high correlation between Ct and Ceq (r = 0.973). Linear regression analysis was used to further investigate this relationship, and a new formula to predict Ceq from Ct was obtained (Ceq = 1.085 Ct + 0.729, R2 = 0.946, SE = 0.49, absolute residuals = 0.38 +/- 0.29 mmol/L). In a validation study (10 HD sessions with new set of urea blood samples) the results obtained by the new formula were compared with measured values of Ceq and those obtained by the Smye formulae. Values predicted by the new formula (9.91 +/- 2.92 mmol/L) were not significantly different from the measured values (10.33 +/- 3.44 mmol/L). Absolute error of the new formula was 0.78 +/- 0.73 mmol/L, median 0.65; ie., 6.93 +/- 5.3%, median 7.7%. Ceq predicted by the Smye formulae (10.95 +/- 4.18 mmol/L) also did not significantly differ from the measured values, but absolute error of predicted values was markedly higher (1.21 +/- 0.90 mmol/L, median 0.89; 11.73 +/- 7.72%, median 10.11%; p < 0.05). When predicted Ceq was used for calculating equilibrated Kt/V (eKt/V), the new formula resulted in lower absolute error (0.09 +/- 0.07, median 0.08) than the Smye method (0.14 +/- 0.08, median 0.12). We conclude that our simple formula is sufficiently accurate in predicting Ceq in standard pediatric HD and that it is more accurate than the existing Smye formulae, while requiring only pre- and post-HD urea samples. We suggest the use of the new formula for predicting Ceq, which can then be used instead of Ct for a more accurate estimation of double pool Kt/V, URR, V, and PCR.

Effects of Postdialysis Urea Rebound on the Quantification of Pediatric Hemodialysis

Urea rebound (UR) causes single pool urea kinetic modeling (UKM), which is based on end-dialysis urea instead of its equilibrated value (Ceq), to erroneously quantify hemodialysis (HD) treatment. We estimated the impact of postdialysis UR on the results of formal variable volume single pool (VVSP) UKM [Kt/V, urea distribution volume (V), urea generation rate (G), normalized protein catabolic rate (nPCR), and urea reduction ratio (URR)] in children on chronic HD. Thirty-eight standard pediatric HD sessions in 15 stable patients (9 female, 6 male) aged 14.5 ± (SD) 3.28 years were investigated. The HD sessions lasted 3.75 ± 0.43 h. The single pool urea clearance was 4.84 ± 1.25 ml/min/kg. All HD sessions were evaluated by VVSP and URR (%) with postdialysis urea taken at the end of HD and with Ceq taken 60 min after the end of HD, incorporating double pool effects and representing true double pool values. The anthropometric V was calculated by Cheek and Mellits formulae for children. VVSP significantly overestimated Kt/V by 0.26 ± 0.18 U (1.68 ± 0.36 vs. 1.42 ± 0.30, p < 0.0001), i.e., 19.05 ± 13.07%, G/V (0.20 ± 0.04 vs. 0.18 ± 0.04, p < 0.0001), nPCR (1.26 ± 0.23 vs. 1.18 ± 0.22 g/kg/day, p < 0.0001), and URR (73.92 ± 6.49 vs. 69.22 ± 7.06, p < 0.0001). VVSP significantly underestimated kinetic V in comparison to anthropometric V (18.74 ± 4.04 vs. 20.76 ± 4.43 liters or expressed as V/body weight: 58 ± 8 vs. 65 ± 9%, p < 0.05), while double pool kinetic V was more accurate (21.45 ± 4.34 liters, V/body weight: 64 ± 6%, p > 0.05). We conclude that UR has a significant effect on all results of UKM even after standard pediatric HD, and the degree of this efffect is documented. We suggest an increase of the minimum required prescribed single pool Kt/V in children and reduction of any delivered single pool Kt/V by approxiamtely 0.26 Kt/V U. Overestimation of nPCR by approximately 0.08 g/kg/day and underestimation of V by 8.5% should be kept in mind.

Orbital pseudotumor in a child on chronic hemodialysis.

Accessible online at: http://BioMedNet.com/karger Dear Sir, Although hemorrhages became less common among renal failure patients after dialysis was introduced, it can still be a diagnostic problem. We report the case history of a uremic girl on chronic hemodialysis who had exaggerated bleeding tendency and clinical manifestations presenting as space-occupying lesion located in the upper third of the left orbita. Since infancy, she had been growth-retarded, enuretic and polyuric. Her mental development was considered to be slightly retarded. When aged 4 years she had the first attack of generalized seizures, but she did not undergo any medical examination. Five years later she was admitted to the local hospital due to a second attack of seizures. She was unconscious, hypertensive and in end-stage renal failure, needed ventilatory support. Peritoneal dialysis was performed. Due to recurrent episodes of peritonitis, she was transferred to University Chil-