An alternative formula to the Cockcroft-Gault and the modification of diet in renal diseases formulas in predicting GFR in individuals with type 1 diabetes

Chronic kidney disease is currently on the rise and not only leads to ESRD necessitating dialysis or transplantation but also increases cardiovascular disease risk. Measurement of the GFR, the gold standard for assessing kidney function, is expensive and cumbersome. Several prediction formulas that are based on serum creatinine are currently used to estimate the GFR, but none has been validated in a large cohort of individuals with diabetes. The performance of two commonly used formulas, the abbreviated Modification of Diet in Renal Disease (MDRD) study formula for the GFR and the Cockcroft-Gault estimate of creatinine clearance, were examined against GFR measured by the renal clearance of iothalamate in 1286 individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT). The performance of these formulas was assessed by computing bias, precision, and accuracy. The DCCT participants had normal serum creatinine, unlike the MDRD patients, and somewhat lower creatinine excretion than subjects in the original cohort Cockcroft Gault, which led to biased and highly variable estimates of GFR when these formulas were applied to the DCCT subjects. The MDRD substantially underestimated iothalamate GFR, whereas the Cockcroft Gault formula underestimated it when it was <120 ml/min per 1.73 m(2) and overestimated it when iothalamate GFR was >130 ml/min per 1.73 m(2). Overall, only one third of the formula's estimates were within +/-10% of iothalamate GFR. By underestimating GFR, these formulas were likely to flag early declines in kidney function. Refitting the MDRD formula to the DCCT data gave a more accurate and unbiased prediction of GFR from serum creatinine; percentage of estimate within 10% of measured GFR increased to 56%. A substantial variability in the estimates, however, remained.     

Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease

The performance of the Modification of Diet in Renal Disease (MDRD) and the Cockcroft-Gault (CG) equations as compared with measured (125)I-iothalamate GFR (iGFR) was analyzed in patients with chronic kidney disease (CKD) and in potential kidney donors. All outpatients (n = 1285) who underwent an iGFR between 1996 and 2003 were considered for analysis. Of these, 828 patients had CKD and 457 were potential kidney donors. Special emphasis was put on the calibration of the serum creatinine measurements. In CKD patients with GFR <60 ml/min per 1.73 m(2), the MDRD equation performed better than the CG formula with respect to bias (-0.5 versus 3.5 ml/min per 1.73 m(2), respectively) and accuracy within 30% (71 versus 60%, respectively) and 50% (89 versus 77%, respectively). Similar results are reported for 249 CKD patients with diabetes. In the kidney donor group, the MDRD equation significantly underestimated the measured GFR when compared with the CG formula, with a bias of -9.0 versus 1.9 ml/min per 1.73 m(2), respectively (P < 0.01), and both the MDRD and CG equations overestimated the strength of the association of GFR with measured serum creatinine. The present data add further validation of the MDRD equation in outpatients with moderate to advanced kidney disease as well as in those with diabetic nephropathy but suggest that its use is problematic in healthy individuals. This study also emphasizes the complexity of laboratory calibration of serum creatinine measurements, a determining factor when estimating GFR in both healthy individuals and CKD patients with preserved GFR.     

Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function

Recent recommendations emphasize the need to assess kidney function using creatinine-based predictive equations to optimize the care of patients with chronic kidney disease. The most widely used equations are the Cockcroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) formulas. However, they still need to be validated in large samples of subjects, including large non-U.S. cohorts. Renal clearance of (51)Cr-EDTA was compared with GFR estimated using either the CG equation or the MDRD formula in a cohort of 2095 adult Europeans (863 female and 1232 male; median age, 53.2 yr; median measured GFR, 59.8 ml/min per 1.73 m(2)). When the entire study population was considered, the CG and MDRD equations showed very limited bias. They overestimated measured GFR by 1.94 ml/min per 1.73 m(2) and underestimated it by 0.99 ml/min per 1.73 m(2), respectively. However, analysis of subgroups defined by age, gender, body mass index, and GFR level showed that the biases of the two formulas could be much larger in selected populations. Furthermore, analysis of the SD of the mean difference between estimated and measured GFR showed that both formulas lacked precision; the CG formula was less precise than the MDRD one in most cases. In the whole study population, the SD was 15.1 and 13.5 ml/min per 1.73 m(2) for the CG and MDRD formulas, respectively. Finally, 29.2 and 32.4% of subjects were misclassified when the CG and MDRD formulas were used to categorize subjects according to the Kidney Disease Outcomes Quality Initiative chronic kidney disease classification, respectively.     

Evaluation of the modification of diet in renal disease study equation in a large diverse population

Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease. Performance of the Modification of Diet in Renal Disease (MDRD) Study equation varies substantially among populations. To describe the performance of the equation in a large, diverse population, estimated GFR (eGFR) was compared to measured GFR (mGFR) in a cross-sectional analysis of 5504 participants in 10 studies that included measurements of standardized serum creatinine and urinary clearance of iothalamate. At eGFR <60 ml/min per 1.73 m(2), the MDRD Study equation had lower bias and higher precision than at eGFR > or =60 ml/min per 1.73 m(2). The accuracy of the equation, measured by the percent of estimates that fell within 30% of mGFR, was similar for eGFR values above or below 60 ml/min per 1.73 m(2) (82% and 84%, respectively). Differences in performance among subgroups defined by age, sex, race, diabetes, transplant status, and body mass index were small when eGFR was <60 ml/min per 1.73 m(2). The MDRD Study equation therefore provides unbiased and reasonably accurate estimates across a wide range of subgroups when eGFR is <60 ml/min per 1.73 m(2). In individual patients, interpretation of GFR estimates near 60 ml/min per 1.73 m(2) should be interpreted with caution to avoid misclassification of chronic kidney disease in the context of the clinical setting.     

Surgical treatment of pulmonary hydatid disease: a comparison of children and adults

Background

Hydatid cyst still remains an important health problem in our country as in many Mediterranean countries. The disease may affect children, and its treatment may be challenging in this age group. Surgery is the primary way of treatment. In the current study, the features unique to childhood pulmonary hydatid disease are emphasized.

Methods

Between 1992 and 2003, 301 patients were operated on because of pulmonary hydatid cyst in our hospital; 44 of them were 14 years or younger. They were categorized as pediatric patients. We retrospectively evaluated the clinical data of the patients.

Results

The mean age of the patients was 10.6 ± 3.7 years (5-14 years) in children and 32.2 ± 14 years (16-75 years) in adults. The rate of intact cyst was 71% in children and 57% in adults (P = .07). The mean diameter of the cyst was 8.5 ± 3.1 cm (3-15 cm) and 6.6 ± 3 cm (2-16 cm) in children and adults, respectively (P < .001). The rate of parenchyme-saving procedures was 84.1% in children, whereas 94.9% in adults. Lobectomy was performed in 16% of children, whereas it was performed in 1.5% of adults (P < .001). Morbidity rates were 13.6% in children and 11.6% in adults. No children but 1 adult died. Long-term follow-up revealed the recurrence rates as 4.5% in children and 4.3% in adults.

Conclusions

Surgery, the primary method of treatment of hydatid cyst, is safe. Parenchyma-saving procedures such as cystotomy and capitonnage should be performed as much as possible. Nevertheless, hydatid cyst can reach relatively larger dimensions in children than in adults, which causes parenchyme destruction eventually leading to lung resection.     

Acacia gum supplementation of a low-protein diet in children with end-stage renal disease

Patients with end-stage renal disease (ESRD) die in the absence of renal replacement therapy (RRT). In developing countries RRT is not uniformly available and treatment often relies on conservative management and intermittent peritoneal dialysis (IPD). This study investigates the possibility of using acacia gum supplementation to improve the quality of life and provide children with ESRD with a dialysis-free period. Three patients referred to our hospital with ESRD during a 3-month period were enrolled in a therapeutic trial to investigate the efficacy of acacia gum (1 g/kg per day in divided doses) as a complementary conservative measure aimed at improving the quality of life. Inclusion criteria included a pre-dialysis creatinine clearance of <5 ml/min, current dietary restrictions and supplementation, at least one dialysis session to control uremic symptoms, absence of life-threatening complications, and sufficient motivation to ensure compliance with the study protocol. One patient complied with the protocol for only 10 days and died after 6 months, despite IPD. Two patients completed the study. Both reported improved well-being. Neither became acidotic or uremic, and neither required dialysis during the study period. Both patients maintained urinary creatinine and urea levels not previously achieved without dialysis. In conclusion, dietary supplementation with acacia gum may be an alternative to renal replacement therapy to improve the quality of life and reduce or eliminate the need for dialysis in children with ESRD in some developing countries.     

Effect of creatinine assay standardization on the performance of Cockcroft-Gault and MDRD formula in predicting GFR.

Sir, The recent article of van Biesen et al. [1] illustrates theimportance of standardization of serum creatinine assays whenusing formulas to estimate glomerular filtration rate (GFR).We provide further proof of the importance     

Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults

Arnon R, Annunziato R, Schilsky M, Miloh T, Willis A, Sturdevant M, Sakworawich A, Suchy F, Kerkar N. Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults.
Clin Transplant 2011: 25: E52–E60. © 2010 John Wiley & Sons A/S. Abstract: Liver transplantation (LT) is lifesaving for patients with Wilson disease (WD) presenting with fulminant hepatic failure (FHF) or chronic liver disease (CLD) unresponsive to treatment. Aim: To determine the outcome of LT in pediatric and adult patients with WD. Methods: United Network for Organ Sharing data on LT from 1987 to 2008 were analyzed. Outcomes were compared for patients requiring LT for FHF and CLD after 2002. Multivariate logistic regression was used to determine risk factors for death and graft loss. Results: Of 90 867 patients transplanted between 1987 and 2008, 170 children and 400 adults had WD. The one‐ and five‐yr patient survival of children was 90.1% and 89% compared to 88.3% and 86% for adults, p = 0.53, 0.34. After 2002, 103 (41 children) were transplanted for FHF and 67 (10 children) for CLD. One‐ and five‐yr patient survival was higher in children transplanted for CLD compared to FHF; 100%, 100% vs. 90%, 87.5% respectively, p = 0.30, 0.32. One‐ and five‐yr patient survival was higher in adults transplanted for CLD compared to FHF; 94.7%, 90.1% vs. 90.3%, 89.7%, respectively, p = 0.36, 0.88. Encephalopathy, partial graft, and ventilator use were risk factors for death by logistic regression. Conclusion: LT is an excellent treatment option for patients with WD. Patients transplanted for CLD had higher patient survival rates than patients with FHF.     

Vegetarian diet: Relevance in renal disease

Summary: Dietary habits are increasingly linked to health and disease. Vegetarian diets have stimulated medical and public interest because vegetarians typically maintain excellent health. In general, their diets are lower in energy, percentage of energy from fat and cholesterol, they have lower bodyweight, blood pressure and plasma lipid levels than omnivores. the vegetarian diet contains sufficient essential amino acids, minerals, and trace elements for optimal nutrition, being deficient only in vitamin B₁₂. the medical possibilities for using vegetable protein as therapy in renal disease are diverse, ranging from treating hyperlipidaemia to protecting the kidney against experimental immune and ablation injury. A vegetarian diet, especially a vegetarian soy diet, has been shown to significantly reduce proteinuria disease progression in diabetic and non-diabetic nephrotic patients. This review summarizes current information about vegetarian and other low protein diets in renal disease which, in the viewpoint of the authors, strongly supports their beneficial role in disease management.     

Pneumococcal vaccine in children and young adults with chronic renal disease

BACKGROUND.: Pneumococcal vaccination has been recommended for immunocompromisedchildren over 2 years including patients with chronic renaldisease. However, the effect of vaccination and revaccinationis variable and the indication for immunization is a subjectof controversy. METHODS.: Forty children and young adults with chronic renal diseases(including the idiopathic nephrotic syndrome, chronic renalfailure, patients undergoing dialysis and after transplantation)were vaccinated with a 23-valent pneumococcal vaccine. The efficacyof the vaccine was evaluated by measuring antibody titres beforeand 4 weeks, 6 months, and 12 months after vaccination. Twenty-twopatients were submitted to a revaccination 1 year after thefirst vaccination. RESULTS.: A sufficient immune response, defined as an at least fourfoldincrease of postvaccinal antibody titres and an antibody titre>200, was observed in 83% of the patients 4 weeks after vaccination,but only in 68% after 6 months, and in 48% after 1 year. Revaccinationproduced a significant immune response in 11/22 patients (50%)followed by a rapid decline of antibody levels within 6 months.Both vaccinations were well tolerated. CONCLUSIONS.: The currently available vaccine is without major side-effectsand effective in producing a significant immune response. Antibodylevels should be monitored in vaccinated patients with chronicrenal diseases considering the rapid decline as early as 6 monthsafter vaccination. Evaluation of the efficacy of revaccinationin these patients requires further investigations.     

Validation of the CKiD formulae to estimate GFR in children post renal transplant

Background

The Chronic Kidney Disease in Children (CKiD) study reported new formulae to estimate glomerular filtration rate (eGFR). The study reported here aimed to assess the accuracy of these formulae in estimating levels and changes in GFR in pediatric renal transplant recipients and generate a new formula in our cohort.

Methods

Two hundred and fifty-two studies of plasma disappearance of ¹²⁵I-iothalamate (C_IO) were used to measure GFR in 155 renal transplant recipients. The CKiD bedside formula (CKiD-BS) was compared with C_IO. A mixed logistic regression model was fit to evaluate the performance of estimating change in posttransplant C_IO using CKiD-BS. We used mixed-effects linear regression to fit a multiplicative model of C_IO. The CKiD cystatin-C-based formula (CKiD-Cys) was also used for comparison in 32 additional transplant recipients. Comparisons were made using Bland–Altman plots.

Results

CKiD-BS underestimates C_IO by 20 % for GFR >25 ml/min per 1.73 m². Percentage change in CKiD-BS performed reasonably well in estimating 15 % change of C_IO beginning 6 months posttransplant [area under the curve (AUC)?=?0.791)] The multiplicative constant in the CKiD-BS was recalibrated [R-Bedside?=?0.461?×?ht(cm)/S_Cr).]A GFR model [GFR-M)?=?10.73?×?[(ht(cm)]0.51/(S_Cr)0.90?×?(BUN)0.23] has higher specificity but similar sensitivity for C_IO compared with R-Bedside. CKiD-Cys overestimates C_IO by 10 ml/min per 1.73 m² across a broad range of GFR.

Conclusions

In our cohort, the CKiD-BS underestimates C_IO; however, changes in CKiD-BS can be used to estimate changes in C_IO. CKiD-Cys overestimates C_IO and is not accurate in estimating C_IO.     

Bladder diverticulum, a congenital disease of children and adults

Genetically all diverticula are congenital and arise from the zone between trigone and detrusor which is susceptible to embryonal disturbances. The climax of the morbidity is in the first and sixth decennium. In both cases, the diverticulum is caused by infravesical obstruction which is congenital in the first group and acquired in the second. The morbidity in the male patient is characteristically higher than in the female. Morphologically, we differentiate between small, medium sized and large diverticula with a gradually increasing morbidity, depending on the size of the diverticulum and involvement of the ipsilateral ureter. The musculature of the diverticular wall is deficient. Pathophysiologically, the growth of a diverticulum depends on three stimuli: an intrinsic one, the exposure to micturitional pressures and a coincidental infravesical obstruction. The micturition has lost its efficiency and is incomplete. The urine in the diverticulum empties incompletely into the urinary bladder. Correlated pathologies include reflux and tendencies towards chronic inflammation and malignant degeneration. Therapeutically, an endoscopic incision of a narrow diverticular neck should be considered first. If this is not sufficient diverticulectomy should be considered next and this is the treatment of choice for large diverticula. No treatment is necessary for small diverticula. If a paraostial diverticulum in children causes reflux of marked degree, the reflux should be operated on by an extravesical approach, sinking the diverticulum into the urinary bladder and eliminating the diverticulum this way.     

Estimation of glomerular filtration rate based on the modification of diet in renal disease equation in patients with chronic renal failure

The list of indications for initiating regular dialysis treatment includes residual glomerular filtration rate (GFR). Under the current European Best Practice Guidelines for Hemodialysis, residual GFR (and the presence of one or more symptoms of uremia) should not decrease below 15 ml/min. The present article seeks to determine to what extent the modification of diet in renal disease (MDRD) equation enables the detection of this decrease in GFR. We tried to answer this question using a more detailed analysis of the relationship between MDRD and renal inulin clearance (C in). Residual GFR based on C in (under conditions of stable plasma levels and water loading) and GFR calculated using the MDRD equation was measured in 79 individuals with chronic renal failure (with mean C in = 19.1 +/- 10.1 ml/min/1.73 m2). Statistical evaluation was performed using regression analysis, the interchangeability of both methods (Bland-Altman) and receiver-operating characteristic (ROC) curve analysis. Regression analysis demonstrated a significant correlation between MDRD and C in (r = 0.892; p < 0.001). However, the regression equation line for the correlation differs significantly from the identity line (p < 0.001). The value of the regression coefficient (0.722) is significantly lower than 1.0 (CI50 0.63; 0.81). The mean MDRD -C in difference was 3.26 +/- 4.46 ml/min/1.73 m2 and the value was significantly different from zero (p < 0.001). The mean difference +2 SD was 12.2 ml/min/1.73 m2, and the mean - 2 SD was -5.7 ml/min/1.73 m2. ROC curve analysis (for a cutoff C in = 15 ml/min/1.73 m2) indicates an area under the curve (AUC) of 0.954 +/- 0.023. The best combination of sensitivity and specificity was obtained for a MDRD of 19.7 ml/min/1.73 m2, with a sensitivity of 90.5% and specificity of 87.5%. For cutoff value of C in = 10 ml/min/1.73 m2, the AUC was 0.939 +/- 0.026 (CI95 0.863-0.890). A combination of maximum sensitivity and specificity was obtained with an MDRD of 16.5 ml/min/1.73 m2. With this value, MDRD sensitivity was 100% and specificity 81.5%. A significant correlation between the MDRD equation and the measured creatinine clearance (C cr) was found (r = 0.883, p < 0.001). The mean difference of MDRD-C cr was -7.2 +/- 6.5 ml/min/1.73 m2. This is significantly different from that of MDRD-C in (p < 0.001). Our results suggest that MDRD and C in in individuals with chronic renal failure are not interchangeable methods for a GFR <15 ml/min/1.73 m2 determination. However, MDRD may furnish valuable information in terms of detecting a critical decrease in GFR; but, the MDRD equation for this decrease in GFR (15 ml/min/1.73 m2) will provide a somewhat higher value (19.7 ml/min/1.73 m2).