Nonasthmatic Churg-Strauss syndrome superimposed on chronic pyelonephritis: a case report.

Churg-Strauss syndrome (CSS) is a granulomatous small-vessel vasculitis. Asthma is seen in the majority of patients with CSS, but atypical nonasthmatic forms of CSS are also being recognized. We herein describe a 67-year-old woman with a history of chronic pyelonephritis and drug allergy reactions who was admitted to our hospital because of worsening renal function preceded by fever, purpura, sinusitis, and a positive urine culture that confirmed a urinary infection. She was initially treated with pipemidic acid for 7 days, followed by clarithromycin for sinusitis. Laboratory tests on admission showed an absolute eosinophil count of 1750 cells/µL and serum creatinine concentration of 4.72 mg/dL. Urine and blood cultures showed no growth. Kidney biopsy revealed crescent formations with diffuse interstitial fibrosis and foci of eosinophil infiltration. An atypical form of CSS was diagnosed based on tissue eosinophilia, peripheral eosinophilia, and sinusitis. Intravenous methylprednisolone and cyclophosphamide pulse therapy together with hemodialysis treatment improved the patient's clinical condition but did not resolve the kidney damage. The onset of an atypical form of CSS in our patient manifested as symptoms and signs mimicking those of chronic pyelonephritis and drug allergy reactions. The patient's chronic kidney disease finally progressed to dialysis dependence.

Comparison of accepted and unaccepted living kidney donors: one-center experience.

BACKGROUND: Kidney transplantation from living donors (LD) has stagnated in many countries. This study aimed to check whether correction of LD selection practice could increase the number of kidney transplantations. METHODS: From January 2003 to December 2012, 241 potential adult LD were evaluated in our hospital. Outcome (mortality and end-stage renal disease-ESRD) of accepted LD (182) was compared with unaccepted (59) donors. RESULTS: Mortality of LD was comparable with that for the standardized Serbian population (SMR = 1.104; 95% CI (0.730-1.606). Among evaluated potential LD, almost every fourth had been unaccepted, but reasons were modifiable in 42.4% of them. In pre-donation period unaccepted donors were significantly older, measured glomerular filtration rate was lower, with higher 15-year and lifelong projected ESRD risks than accepted donors. Despite this, ten years outcome of both groups LD was similar: none of LD developed ESRD, 9.8% of accepted and 11.8% of unaccepted LD died (p = .803). CONCLUSIONS: During an average of 101 months of follow-up mortality of accepted LD did not differ significantly as compared to the age standardized Serbian population and none of them developed ESRD. In examination of potential LD, the use of accurate and precise methods for kidney function estimation and the evaluation of risk for ESRD and mortality as well as treatment of modifiable contraindications for kidney donation are necessary.

Cystatin C and serum creatinine as predictors of kidney graft outcome.

PURPOSE: Serum cystatin C (Cys C) was evaluated as a predictor of kidney graft failure progression, and its predictive ability was compared to other markers of graft function. METHODS: The following kidney graft markers were determined in 91 patients who came for regular checkups of kidney graft function to our outpatient service in February 2008: Cys C, serum creatinine (sCr), 24-h proteinuria and 24-h urinary creatinine clearance (CCr). Glomerular filtration rate (eGFR) was estimated using sCr-based and Cys C formula. Patients were regularly monitored until February 2013 or to graft failure. RESULTS: During follow-up, graft failure occurred in 21 recipients. The Cys C ≥2.65 mg/l discriminated patients with and without graft failure (sensitivity of 80.95% and specificity of 92.86%). According to c statistic, the highest performance was achieved for Cys C (0.874). In addition, Cys C area under the curve (AUC) was significantly better than CCr AUC (p = 0.007), 24-h proteinuria AUC (p = 0.03), eGFR estimated by the chronic kidney disease epidemiology collaboration (EPI) AUC (p = 0.05), but not better than sCr or eGFR AUCs calculated by other formulas. In the multivariable model, sCr, CCr, Cys C and eGFRs were predictors of graft failure. Combination of Cys C, sCr and logarithm of 24 h proteinuria (0.883) or Cys C, CCr and logarithm of 24-h proteinuria (0.884) had the highest AUC for predicting graft outcome that exceed insignificantly Cys C or sCr areas. CONCLUSIONS: The most reliable predictors of graft outcome were Cys C, sCr and proteinuria. Because Cys C is unavailable in many transplant centers, from the practical point of view, sCr remains the most sensitive predictor of graft outcome.

[Is morning urinary protein-to-creatinine ratio a reliable estimator of 24-hour proteinuria in patients with kidney diseases?].

INTRODUCTION: Proteinuria is the most frequent marker of kidney damage. Although 24-hour urinary proteinuria is the gold standard, the measurement of proteinuria from albumin urinary creatinine ratio is proposed as much useful method. OBJECTIVE: To evaluate the accuracy of urine protein-to-creatinine (P/Cr) ratio in morning urine specimens as compared with 24-hour total protein excretion for the measurement of proteinuria in patients with different kidney diseases and different renal function levels. METHODS: Proteinuria in the studied patients was assessed by 24-hour protein excretion (24-hour PRT) and spot urine P/Cr ratio. The analysis of concordance between 24-hour PRT and P/Cr was carried out using intraclass correlation coefficient (ICC), paired t-test and Bland-Altman plots. The discriminant cutoff values for spot urine P/Cr ratio in predicting 24-hour protein "threshold" excretion were determined using receiver operating characteristic curves (ROC), as well as sensitivity and specificity. RESULTS: A total of 303 patients were included in the study. The concordance between 24-hour PRT and P/Cr ratio was excellent (ICC 0.931). Systematic overestimation of PRT by urinary P/ Cr ratio was disclosed (mean difference 0.138, p = 0.011). The P/Cr of 0.25 (sensitivity 0.90; specificity 0.96), 0.66 (1.00; 0.91) and 2.55 (1.0; 0.97) g/g reliably predicted 24-hour urine total protein equivalent "thresholds" at 0.2, 1.0 and 3.5 g/day. The chronic renal failure group independently positively influenced the difference between 24-hour PRT and P/Cr. It means the lower the kidney function the higher is the difference between the two proteinuria measurements. CONCLUSION: This study supports the recommendation of using spot urine P/Cr ratio in proteinuria screening in patients with different kidney diseases. The obtained results indicated better agreement between morning P/Cr and 24-hour PRT in patients with lower proteinuria and better kidney function.

Fast and efficient in silico 3D screening: toward maximum computational efficiency of pharmacophore-based and shape-based approaches.

In continuation of our recent studies on the quality of conformational models generated with CATALYST and OMEGA we present a large-scale survey focusing on the impact of conformational model quality and several screening parameters on pharmacophore-based and shape-based virtual high throughput screening (vHTS). Therefore, we collected known active compounds of CDK2, p38 MAPK, PPAR-gamma, and factor Xa and built a set of druglike decoys using ilib:diverse. Subsequently, we generated 3D structures using CORINA and also calculated conformational models for all compounds using CAESAR, CATALYST FAST, and OMEGA. A widespread set of 103 structure-based pharmacophore models was developed with LigandScout for virtual screening with CATALYST. The performance of both database search modes (FAST and BEST flexible database search) as well as the fit value calculation procedures (FAST and BEST fit) available in CATALYST were analyzed in terms of their ability to discriminate between active and inactive compounds and in terms of efficiency. Moreover, these results are put in direct comparison to the performance of the shape-based virtual screening platform ROCS. Our results prove that high enrichment rates are not necessarily in conflict with efficient vHTS settings: In most of the experiments, we obtained the highest yield of actives in the hit list when parameter sets for the fastest search algorithm were used.

Co-morbidity and kidney graft failure-two main causes of malnutrition in kidney transplant patients.

BACKGROUND: Malnutrition is very frequent in chronic renal failure but, after successful kidney transplantation, body weight gain is common and is widely investigated, while malnutrition after transplantation is underestimated. In the present study, the prevalence of malnutrition in kidney transplant patients and the factors which might contribute to its development are analysed. METHOD: In a population of 452 kidney transplant patients followed-up regularly at our department, body mass index (BMI) was determined. Out of this population, 47 patients (18 females, aged 13-54 years, post-transplantation period 6-180 months) were randomly selected for more detailed examination of their nutritional status using anthropometry (body weight, the mid-arm muscle circumference, skinfold thickness, BMI) as well as biochemical parameters (serum protein, albumin, cholesterol, red blood cell count). Co-morbidity of the selected patients was assessed using the Index of Coexistent Diseases. RESULTS: Among 452 kidney transplant patients, 15% had a BMI of <21 kg/m(2), 45% had a BMI of 21-25 kg/m(2), and 40% had a BMI >25 kg/m(2). After more accurate assessment of nutritional status of the selected 47 patients, a comparison between those who were malnourished (11 patients) and those who were well nourished (20 patients) was made. No significant difference was found in age at transplantation, pre-transplantation time on dialysis, donor origin, early post-transplant course, immunosuppressive therapy, number of rejection episodes or post-transplant period between these two groups. However, malnutrition appeared significantly more frequently in females, and malnourished patients had significantly higher serum creatinine levels. Co-morbidity conditions, assessed by the Index of Disease Severity and Index of Physical Impairment combined peak scores resulting in the final Index of Coexistent Disease, were more frequent and more severe in malnourished patients as compared with well-nourished patients. CONCLUSION: In a population of kidney transplant patients regularly followed-up at our clinic, 15% had malnutrition. Malnutrition is more frequent in females, but kidney graft failure and co-morbidity had a significant role in its development.

[Analysis of living related kidney donors and their postoperative course]. / Izbor zivih srodnih davalaca za transplantaciju bubraga i njihov postoperacioni tok.

Lack of cadaveric organs for transplantation resulted in increased number of living related kidney donors examinations and consequent transplantations in our Department. Donor procedure, selection, drop-outs and final results for living related donors (LRD) were retrospectively analyzed in this paper. Between 1987 and 1994 202 potential LRD were examined. Most of them were females (59%) and about 30% were older than 60 years. The family relation between LRD and recipients were: parents (95%), siblings (3%), grandmother/grandfather (1.5%) and uncle (0.5%). Potential LRD were informed on risks, advantages and procedure of living donor transplantation. After primary information 26% of potential LRD gave up further examinations. Following immunological and clinical evaluations 48% of LRD actually donated a kidney. The other 26% were excluded during the selection procedure. High immunological risks including ABO incompatibility, HLA mismatches and positive cross match test were the reasons for drop outs of 35 potential LRD (17%). Five more donors were excluded for medical reasons: one because of low creatinine clearance and four because of neoplasms, discovered during examination (kidney, laryngeal, lung). Fourteen transplantation were not realized due to different recipient reasons: 5 of them had clinical contraindications, two died and in 7 cadaveric kidney transplantations were performed. Mild hypertension, coronary disease and diabetes mellitus type 2 were presented in 5 LRD accepted for transplantation. Five more had to be operated before donation (abdominal or urological operation). Early complications after donor nephrectomy were acute renal failure, stress ulcus, pleuropneumonia in three and thromboflebitis in two donors. In conclusion, although kidney transplantation from LRD is highly successful, careful examination during selection procedure is indispensable.