Nuclear Glomerular Filtration Rate Research Articles

Pre-transplant glomerular hyperfiltration is not a risk factor for increased renal morbidity and mortality in pediatric stem cell transplant patients.

Low glomerular filtration rate (GFR) prior to stem cell transplant (SCT) is associated with increased morbidity and mortality. The implications of abnormally high GFRs, or glomerular hyperfiltration, prior to SCT are unknown. Twenty-two of 74 consecutive pediatric SCT patients over 2years old at a single center were hyperfiltrating prior to SCT, median nuclear medicine GFR 154mL/min/1.73m2 [interquartile range: 146-170]. There was no association between hyperfiltration and any transplant demographics, nor between hyperfiltration and acute kidney injury (p=.8), renal replacement therapy (p=.63), 1-year event-free survival (p=1), or abnormal creatinine-based estimated GFR at a median follow-up of 4.7years (p=.73).

An Unusual Case of Low Vancomycin Exposure Despite Extremely High Vancomycin Doses Accompanied by Renal Toxicity: A Grand Round.

This grand round describes the case of a patient who received 10 grams (143.5 mg/kg) of vancomycin every 24 hours via continuous infusion, in whom the highest observed level was only 15.4 mg/L. Despite subtherapeutic levels, renal impairment was encountered, which resolved after the discontinuation of vancomycin. Glomerular hyperfiltration was found through nuclear glomerular filtration rate measurement, which likely explains the need for high doses (>6 grams per 24 hours continuous infusion) without reaching therapeutic serum levels.

Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers

BackgroundCarboplatin remains integral for treatment of gynaecological malignancies and dosing is based on glomerular filtration rate (GFR). Measurement via radiotracer decay [nuclear medicine GFR (nmGFR)] is ideal. However, this may be unavailable. Therefore GFR is often estimated using formulae that have not been validated in patients with cancer and/or specifically for gynaecological malignancies, leading to debate over optimal estimation. Suboptimal GFR estimation may affect efficacy or toxicity.MethodsWe surveyed several UK National Health Service Trusts to assess carboplatin dosing practise. We then explored single-centre accuracy, bias and precision of various formulae for GFR estimation, relative to nmGFR, before validating our findings in an external cohort.ResultsAcross 18 Trusts, there was considerable heterogeneity in GFR estimation, including the formulae used [Cockcroft–Gault (CG) versus Wright], weight adjustment and area under the curve (AUC; 5 versus 6). We analysed 274 and 192 patients in two centres. Overall, CamGFR v2 (a novel formula for GFR estimation developed at Cambridge University Hospitals NHS Foundation Trust) excelled, showing the highest accuracy and precision. This translated into accuracy of hypothetical carboplatin dosing; nmGFR-derived carboplatin dose fell within 20% of the Cam GFR v2-derived dose in 86.5% and 87% of patients across the cohorts. Among the CG formula and its derivatives, using adjusted body weight in those with body mass index ≥25 kg/m2 [CG-adjusted body weight (CG-AdBW)] was optimal. The Wright and unadjusted CG estimators performed most poorly.ConclusionsWhen compared with nmGFR assessment, accuracy, bias and precision varied widely between GFR estimators, with the newly developed Cam GFR v2 and CG-AdBW performing best. In general, weight (or body surface area)-adjusted formulae excelled, while the unadjusted CG and Wright formulae or the use of AUC6 (versus nmGFR AUC5) produced risk of significant overdose. Thus, individual centres should validate their GFR estimation methods. In the absence of validation, CG-AdBW or CamGFR v2 is likely to perform well while unadjusted CG/Wright formulae or AUC6 dosing should be avoided.

Residual kidney function in nocturnal vs conventional haemodialysis patients: a prospective observational study.

Residual kidney function (RKF) provides substantial volume and solute clearance even after dialysis initiation. Preservation of RKF is associated with improved outcomes including mortality in patients on both peritoneal and haemodialysis (HD). Factors predicting RKF loss are unclear, including HD modality. Nocturnal haemodialysis (NHD) may result in less aggressive fluid and solute shifts, however, retrospective data suggests frequent NHD may accelerate RKF decline. The aim of the study was to determine if decline in RKF differs between patients undergoing conventional haemodialysis (CHD) versus NHD. A prospective observational study of incident HD patients was undertaken comparing patients undertaking CHD (4-5h, 3days/week) and NHD (8h, 3-5 nights/week). Change in RKF was measured by urea and creatinine clearance (48-h interdialytic urine collection) and glomerular filtration rate (GFR) (Cr51-EDTA nuclear scan) at initiation of dialysis (baseline) and 12months. A total of 18 incident HD patients were recruited (8 CHD, 10 NHD). Three patients withdrew after baseline (n = 15). Baseline RKF was similar between groups with mean nuclear GFR of 13.3 ± 4.1mL/min in the CHD cohort vs 13.5 ± 4.6mL/min in the NHD group (p = 0.89). Baseline urine volume was 2399 ± 950mLs and 2794 ± 1662mLs in the CHD and NHD, respectively (p = 0.57). Nuclear GFR declined from time 0 to 12months to 9.3 ± 2.5mL/min and 10.4 ± 4.3mL/min in the CHD and NHD, respectively (p = 0.52). There was a significant decline in 48-h urine volume over 12months with a mean volume of 1943 ± 1087.0mLs in the CHD compared to 601.7 ± 315.3mLs in the NHD (p = 0.01). No significant difference was found in other measures of RKF between groups over 12months. This small prospective cohort study found that the loss of residual urine volume was greater in the NHD vs the CHD cohort but there was no difference in other measures of RKF.

Fundamental problems with pediatric adaptive dosing of carboplatin using nuclear-medicine-based estimates of renal function.

Carboplatin is often adaptively dosed based on glomerular filtration rate (GFR), usually estimated by nuclear medicine tests. At least five pediatric adaptive dosing formulas have been developed. In an effort to standardize dosing in Children's Oncology Group protocols, we explored methodologic variation in GFR estimation and adaptive-dosing formula performance. Nuclear medicine GFR data from published series of ≥100 children with cancer were compared. Data from patients for whom body surface area, weight, GFR, and tracer half-life were available were used to compare formulas. Differences in methods used to estimate GFR in children with cancer resulted in highly variable population results, with median GFRs ranging from 96 to 150mL/min/1.73m2 . The choice of adaptive formula had a major impact on calculated dose. When targeting an area under the curve of 7.9mg/mL • min, the median difference between the formula yielding the lowest and highest carboplatin dose for individual subjects was 289 (range 96-1737) mg/m2 . Wide variation in GFR obtained with nuclear-medicine-based tests in children with cancer primarily results from systematic methodologic errors. Formulas for calculating carboplatin dose produce additional and substantial variation that may place children with cancer at unnecessary risk for excessive toxicity or underdosing. These findings indicate a need for the development of a uniform, validated method for GFR determination in children that should be utilized in all centers. Currently, adaptive dosing of carboplatin based on GFR has serious limitations and in most clinical settings should arguably not be used in place of body-surface-area-based dosing.

Validation of serum creatinine-based formulae in pediatric renal transplant recipients.

BackgroundAccurate monitoring of kidney function is important post-renal transplant; however, the routine use of measured glomerular filtration rate (GFR) or addition of newer serum markers is prohibitively expensive for routine clinical use, especially in children. We validated the modified Schwartz formula in pediatric renal transplant recipients across a range of demographic and clinical characteristics.MethodsIn a retrospective cohort study with nested cross-sectional analysis, we compared 505 measurements of estimated GFR using serum creatinine to simultaneous diethylenetriaminepentaacetic acid (DTPA) nuclear GFR (nGFR) measurements from 173 pediatric kidney transplant recipients who were < 18 years of age from 1 January 2001 to 31 December 2012 accounting for repeated measures.ResultsAmong 173 children, 62% were males, 85% with nGFR of ≥60 ml/min/1.73 m2, and the median age at transplant was 13.6 years (interquartile range 8.3-16 years). Overall, the modified Schwartz and Pottel formulae had better bias (0.07 and -0.03 ml/min/1.73 m2, respectively) and accuracy within 30% (both 84.4%) in comparison to Lyon and Zappitelli formulae. The 30% accuracy varied for girls and children <5 and >15 years.ConclusionModified Schwartz is a practical, non-invasive, and a valid bedside tool that provides a valid measurement of GFR in pediatric kidney transplant recipients.

Efficacy, Side Effects, and Monitoring of Oral Cyclosporine in Interstitial Cystitis-Bladder Pain Syndrome

To evaluate the efficacy of oral cyclosporine A (CyA) in the treatment of refractory interstitial cystitis-bladder pain syndrome (IC-BPS) and to assess safety using drug level and renal function monitoring. Patients with IC-BPS who failed at least 2 prior treatments were enrolled in an open-label study of oral CyA. Medication was started at 3 mg/kg divided twice daily for 3 months. Dose was adjusted based on side effects and the drug level was measured 2 hours after the morning dose (C2). The primary end point was moderate or marked improvement of global response assessment or >50% improvement on the Interstitial Cystitis Symptom Index (ICSI) or Interstitial Cystitis Problem Index at 3 months. Twenty-two of 26 patients completed the 3-month follow-up; 18 completed the poststudy evaluation. The median symptom duration was 66 months (12-336). At 3 months, 31% (8/26) improved by global response assessment, 15% (4/26) had >50% improvement in the ICSI score, and 19% (5/26) had an improvement in the Interstitial Cystitis Problem Index score. Hunner lesions (HLs) predicted an improvement in the ICSI score (odds ratio = 15.4, 95% confidence interval: 1.7-224.6, P = .01), with 75% (3/4) of the responders having HL. Two patients withdrew because of hypertension or elevated serum glucose. The mean nuclear glomerular filtration rate declined at 3 months (98.9 ± 31.6 vs 84.2 ± 25.5 mL/min/1.73 m2, P = .01) and reversed to baseline after discontinuation of treatment. C2 levels did not correlate with symptoms but allowed dose reduction in 11 patients. Per American Urological Association guidelines, CyA can be effective in a proportion of patients with refractory IC-BPS. Patients with HL are more likely to benefit. Monitoring of C2 rather than trough levels can lead to dose reduction, thereby minimizing toxicity.

A comparison of renal responses to sevoflurane and isoflurane in patients undergoing donor nephrectomy: a randomized controlled trial.

Sevoflurane and isoflurane are volatile halogenated ether widely used in anesthesia. Both have comparable potency and easy titratability but sevoflurane has lower pungency and results in faster patient recovery. Isoflurane, however, is more affordable. The nephrotoxicity of sevoflurane is undisputed but studies on isoflurane nephrotoxicity are lacking. The objective of this paper is to determine the overall nephrotoxicity profile of sevoflurane and isoflurane in donor nephrectomy patients using the renal function markers – nuclear glomerular filtration rate (GFR), serum creatinine, urine protein-to-creatinine ratio, proteinuria, and glucosuria. A randomized comparative study of postoperative renal functions in donor nephrectomy patients who had received either low-flow (< 1 L/min) sevoflurane or isoflurane were analyzed. The renal parameters were repeated 72 hours post anesthesia. Forty-seven subjects (46%) were randomized to receive isoflurane while fifty-five received sevoflurane (54%). Between the two anesthetic groups, there was no significant difference in terms of serum creatinine, total GFR, or nuclear GFR. There was a statistically higher proportion of patients with urine protein-to-creatinine ratios of 0.2 and above in the isoflurane group (64% vs. 38%), while more patients in the sevoflurane group had ratios above 0.2 (62% vs. 36%, P < 0.05). The type of anesthetic agent was not an independent predictor of increasing serum creatinine, total GFR and urine protein-to-creatinine ratio and nuclear GFR. In conclusion, the overall nephrotoxicity profile of sevoflurane and isoflurane-treated donor nephrectomy patients is minimal.

Estimated versus Measured Glomerular Filtration Rate in Children before Hematopoietic Cell Transplantation

An accurate assessment of kidney function before hematopoietic cell transplantation (HCT) can help to properly dose conditioning chemotherapy and follow patients for the development of chronic kidney disease. We cross-sectionally examined 94 children and young adults before HCT to compare formal nuclear glomerular filtration rate (GFR) testing with estimated GFR using creatinine and cystatin C–based equations, including the original Schwartz formula and the more recent formulas developed in the Chronic Kidney Disease in Children (CKiD) cohort. The median age of the cohort was 5.9 years (range, .26 to 30.5 years). The mean cohort nuclear GFR was 107.4 ± 24.7 mL/min/1.73 m2, with 18 of 94 subjects (19.1%) having abnormal kidney function (GFR < 90 mL/min/1.73 m2) before HCT. The creatinine-based original Schwartz and bedside CKiD formulas showed significant bias, overestimating the nuclear GFR by 57.4 (95% confidence interval [CI], 49.0 to 65.8) and 14.1 (95% CI, 7.1 to 21.1) mL/min/1.73 m2, respectively. Cystatin C formulas had less mean bias and improved accuracy but also had decreased sensitivity to detect abnormal kidney function before HCT. The Full CKiD equation showed the best performance, with a mean bias of −3.6 mL/min/1.73 m2 (95% CI, −8.4 to 1.2) that was not significantly different from the measured value and 87.7% of estimates within ±30% of the nuclear GFR. Although the more recent bedside CKiD formula performed better than the original Schwartz formula, both formulas had poor sensitivity for detecting a low GFR. An abnormal pretransplant nuclear GFR was not associated with post-HCT acute kidney injury, the need for dialysis, or death in the first 100 days. In conclusion, we observed cystatin C–based equations outperformed creatinine-based equations in estimating GFR in children before HCT. However, all formulas had decreased sensitivity to detect impaired GFR. Formal measurement of kidney function should be considered in children and young adults who need an accurate assessment of kidney function before HCT.

Performance of cystatin C-based equations in a pediatric cohort at high risk of kidney injury

Limited data exist on the performance of cystatin C-based glomerular filtration rate (GFR) equations in pediatric transplant recipients and other high-risk patients. The aim of our study was therefore to evaluate the performance of current cystatin C-based equations in this population. This was a retrospective, cross-sectional study of 141 consecutive patients (58 % post-transplant) who received a nuclear medicine GFR (NucGFR) examination using (99m)Tc- diethylenetriaminepentaacetic acid at our institution. Subjects included children receiving liver, kidney or hematopoietic stem cell transplants and patients with oncologic or urologic disease. GFR estimates using published GFR estimating equations, including those based on cystatin C (Filler, Zappitelli, Larsson, Hoek, Rule and Le Bricon equations, respectively) and on both cystatin C and creatinine (Zappitelli, Bouvet and Schwartz equations, respectively), were evaluated and compared to the NucGFR measurement using Bland-Altman analysis. The mean NucGFR was 95 (interquartile range 76-111) ml/min/1.73 m(2). Of the cystatin C-based equations, the Rule, Hoek, Zappitelli and Schwartz (2009 CKiD equation) formulas provided the closest agreement to the NucGFR estimate. All other formulas overestimated the GFR in our cohort. Cystatin C-based GFR formulas can provide an accurate estimation of NucGFR in a pediatric population with a high proportion of transplant recipients and oncology patients.

Cystatin C-estimated Glomerular Filtration Rate in Pediatric Autologous Hematopoietic Stem Cell Transplantation

Formal evaluation of kidney function is essential to determine chemotherapy dosing based on established treatment protocols in children undergoing autologous stem cell transplantation. Cystatin C has been widely studied as a marker of the glomerular filtration rate (GFR), although data regarding its use in stem cell transplantation are limited. We evaluated the performance of cystatin C-based equations and determined their sensitivity to detect a nuclear GFR of <100 mL/min/1.73 m(2) in children undergoing autologous transplantation. We performed a retrospective cohort analysis in 16 children undergoing 26 transplantations using a modified Bland-Altman analysis to account for repeated measures. Cystatin C-based equations published by Hoek, Le Bricon, Rule, Filler, Zappitelli, Larsson, and Schwartz (the New Chronic Kidney Disease in Children formula, New CKiD formula) were evaluated and compared to the creatinine-based modified Schwartz equation. We found that cystatin C-based equations demonstrated improved sensitivity to detect a nuclear GFR of <100 mL/min/1.73 m(2) compared to the creatinine-based modified Schwartz equation, which significantly overestimated GFR. Most cystatin C-based equations, however, tended to underestimate the nuclear GFR. The New CKiD formula, combining cystatin C and creatinine, offered a sensitivity of 100% and a specificity of 95% for detecting a nuclear GFR <100 mL/min/1.73 m(2). Institutions using cystatin C-based GFR estimation should be aware of the specific prediction formula and GFR measurement techniques available at their center, as each method's performance can vary considerably. As more research becomes available, this easily measured marker should become a valuable component of GFR estimation, providing cost savings (a nuclear GFR is 5.5 times more costly than a cystatin C) and reducing radiation exposure.

Performance of the creatinine-based and the cystatin C-based glomerular filtration rate (GFR) estimating equations in a heterogenous sample of patients referred for nuclear GFR testing

Cystatin C may be a more accurate marker of the glomerular filtration rate (GFR) than creatinine. We evaluated the performance of the creatinine-based abbreviated modification of diet in renal disease (MDRD), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and 6 cystatin C-based equations in estimating GFR (eGFR) in a heterogeneous sample of patients. Measured GFR (mGFR) was obtained from the plasma clearance of 99mtechnetium Diethylenetriaminepentaacetic acid in 42 adult patients referred for nuclear GFR testing (January to March 2008). We evaluated the bias, precision, and accuracy of the abbreviated MDRD, CKD-EPI, Filler, Grubb, Hoek, Larsson, Le Bricon, and Rule eGFR equations. Participants had a mean mGFR of 70.9 mL/min/1.73 m2 (range: 22-125 mL/min/1.73 m2), a median age of 57 years (interquartile range: 45, 66), were 62% male, and were 38% liver transplant recipients. Correlation coefficients between eGFRs and mGFR ranged from 0.65 to 0.87 (each P<0.001). The cystatin C-based Hoek equation had the best overall performance with a low bias (-1.4 mL/min/1.73 m2), good precision (13.3 mL/min/1.73 m2), and greatest accuracy, with 93% of values within 30% of mGFR. Although the CKD-EPI equation had the lowest bias (-0.6 mL/min/1.73 m2), it had poor precision (20.7 mL/min/1.73 m2) and low accuracy, with only 69% of values within 30% of mGFR. The Hoek equation remained accurate and had the least bias when patients were grouped according to the history of liver transplantation and the mGFR above or below 60 mL/min/1.73 m2. In this heterogeneous sample, the cystatin C-based Hoek equation performed the best overall, regardless of mGFR level or history of liver transplantation.

Early clinical indicators of transplant-associated thrombotic microangiopathy in pediatric neuroblastoma patients undergoing auto-SCT

Patients undergoing auto-SCT for neuroblastoma present a unique population to study transplant-associated thrombotic microangiopathy (TA-TMA), due to standardized chemotherapy and later exposure to radiation and cis-retinoic acid (cis-RA). We retrospectively analyzed 20 patients after auto-SCT to evaluate early clinical indicators of TA-TMA. A total of 6 patients developing TA-TMA (30% prevalence) were compared with 14 controls. Four of six patients were diagnosed with TA-TMA by 25 days after auto-SCT. Compared with controls, TA-TMA patients had higher average systolic and diastolic blood pressure levels during high-dose chemotherapy and developed hypertension by day 13 after auto-SCT. Proteinuria was a significant marker for TA-TMA, whereas blood and platelet transfusion requirements were not. Serum creatinine did not differ between groups post transplant. However, patients with TA-TMA had a 60% decrease in renal function from baseline by nuclear glomerular filtration rate, compared with a 25% decrease in those without TA-TMA (P=0.001). There was no TA-TMA-related mortality. Significant complications included end-stage renal disease (n=1) and polyserositis (n=3). Patients with TA-TMA were unable to complete cis-RA therapy after auto-SCT. We suggest that careful attention to blood pressure and urinalysis will assist in the early diagnosis of TA-TMA, whereas serum creatinine seems to be an insensitive marker for this condition.

The inaccuracy of cystatin C and creatinine-based equations in predicting GFR in orthotopic liver transplant recipients

As survival with an orthotopic liver transplant (OLT) improves, the incidence of chronic kidney disease in OLT recipients increases. Measurement of kidney function using creatinine-based estimates is often inaccurate, while cystatin C may overcome the biases that effect creatinine. The aim of this study was to assess the accuracy of creatinine- and cystatin C-based equations to estimate kidney function in long-term OLT recipients. This was a cross-sectional study performed on OLT recipients within a single liver transplant centre where creatinine (n = 41) and cystatin C (n = 30) were measured and glomerular filtration rate (GFR) estimated using the Modification of Diet and Renal Disease (MDRD), Cockcroft-Gault (CG), Hoek, Larsson, Filler and Le Bricon equations. Comparison was made with the nuclear GFR (nGFR) (n = 41) measured through 51-Cr EDTA clearance. The mean age of recipients was 56 +/- 13 years, and they were 6.5 +/- 4.7 years post-OLT. Fifty-six percent of recipients had a nGFR < or =60 mL/min/1.73 m(2). nGFR correlated significantly with all predictive equations (P < 0.001). The MDRD, CG and Le Bricon equations had the smallest degree of bias (-7.6, -7.3 and 3.4 mL/min/1.73 m(2), respectively), with 22%, 22% and 27% of estimates, respectively, being within 10% of nGFR measurements. In OLT recipients with nGFR < or =60 mL/min/1.73 m(2), the degree of bias of both the creatinine-base MDRD and cystatin-based Hoek equations was within 2 mL/min/1.73 m(2) difference between the measured and estimated GFR, but 41% and 36% of estimates were within 10% of the nGFR measurement. Therefore, the degree of inaccuracy in cystatin C- and creatinine-based predictive equations brings into question their clinical utility in OLT recipients. We have no evidence that cystatin C is superior to creatinine in this population.

A Comparison of the Predictive Performance of Different Methods of Kidney Function Estimation in a Well-Characterized HIV-Infected Population

Background: Glomerular filtration rate (GFR) estimation equations have never been validated in the HIV population. This pilot study aimed to compare all currently available methods of kidney function assessment with nuclear GFR in HIV-infected adults. Methods: Patients underwent GFR measurement with ^99mTc-diethylenetriaminepentaacetic acid (Tc-99m Pentetate), and measured values were compared with results of creatinine-based estimation equations [abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) formula and Cockcroft-Gault (CG) formulae], 24-hour urine creatinine clearance and estimated cystatin C GFR. Results: Twenty-seven HIV-infected adults were studied. Most were male and Caucasian, with a mean age of 52 years. Median CD4 was 290 cells/mm³, 70% of patients had HIV RNA <50 copies/ml and all were receiving highly active antiretroviral therapy (median 5 drugs). Median Tc-99m Pentetate-GFR was 91 ml/min/1.73 m². Despite greater bias and similar accuracy, the MDRD formula was more precise than the CG formula, regardless of whether CG estimations were corrected for ideal body weight or body surface area. Relative accuracy within 30% of nuclear GFR was greater for the MDRD formula than for all other methods. The performance of 24-hour urine creatinine clearance was similar to that of the MDRD formula for patients with GFR <90 ml/min/1.73 m², although it performed less well at higher GFR. The performance of cystatin C GFR was inferior to that of all the creatinine-based methods. Conclusions: While no method of kidney function estimation performed highly, both 24-hour urine creatinine clearance and the MDRD formula performed with a level of precision and accuracy sufficient for clinical decision making. Our findings support the preferential use of the MDRD formula in the treated HIV population and suggest that there are no HIV-specific factors that limit equation applicability. Larger validation studies are needed to confirm our findings and allow generalization to the HIV population at large.

Influence of commonly used drugs on the accuracy of cystatin C-derived glomerular filtration rate

There is controversy about the effect of certain drugs on cystatin C (CysC) concentrations, which would limit the usability of CysC for estimation of glomerular filtration rate (GFR) in patients with renal disease. Seventy-one children (ages 2.6 months to 18 years) with renal disease and on at least one study medication (tacrolimus, cyclosporine, mycophenolate mofetil, corticosteroids, fosinopril, ramipril and enalapril, losartan, cotrimoxazole) were tested in 85 nuclear medicine GFR clearance studies with simultaneous CysC determinations. We analyzed the relationship between the dose per kilogram and the ratio of the measured GFR to the CysC-derived GFR, with a ratio of 1 resembling agreement. A non-zero slope in linear regression analysis was considered significant for a drug effect on CysC. No significant relationship was found between the doses of the medication and the cystatin C GFR for any of the medications. Only cotrimoxazole showed a GFR ratio that was significantly lower than 1, which may be related to small numbers; otherwise the value was always 1. CysC provides accurate data for calculating GFR independent of the drug doses studied and avoids the use of methods of direct GFR measurement.

Postnatal outcome and natural history of antenatally-detected hydronephrosis

Routine maternal ultrasonography (US) has revealed a very high incidence of fetal hydronephrosis (HDN), the postnatal outcome and management protocols of which are replete with controversies. Pelviureteric junction (PUJ) obstruction is the commonest postnatal diagnosis, and its management has no consensus to date. This study was carried out to define the postnatal outcome and natural history of fetal HDN and to identify the mode of management to be adopted to the best advantage. All patients were subjected to US 48 h postnatally or at first presentation and isotope renography (DTPA) with nuclear glomerular filtration rate (GFR) was carried out at 3-4 weeks of age or at presentation. Micturating cystourethrography (MCU) and/or direct radionuclide cystography (DRCG) were done in cases with bilateral HDN, nonobstructive HDN, dilated ureter on US, and recurrent urinary tract infection. Patients were then grouped for surgical intervention or conservative follow-up. Investigations were repeated periodically. A total of 56 patients were registered for the study (78 renal units) with a mean follow-up period of 14.6 months; 37 renal units were operated upon or scheduled for surgery and 67 had some organic pathology, of which PUJ obstruction was the commonest. Among patients with PUJ obstruction, indications for surgery included symptoms, a palpable mass, poor or deteriorating function, and a solitary functioning kidney. Patients operated upon showed improvement in function and/or drainage, while those followed conservatively remained stable or improved. Controversy still exists as to the optimal management of PUJ obstruction detected antenatally. While it is the commonest postnatal diagnosis, many other pathologies are now being encountered. In antenatally-diagnosed HDN, there is a good scope for conservative management provided rigid follow-up can be ensured, especially because a good recovery potential exists followed surgery whenever indicated.

Modification of the 8 drugs in 1 day regimen: feasibility of substitution of other agents

Six children (ages 2 to 14 years) with recurrent or poor risk primary brain tumors were treated with the '8 drugs in 1 day' chemotherapy regimen. As renal function deteriorated (median after five cycles), carboplatin was substituted in place of cisplatin at a median dose of 300 mg/m2 as a one hour infusion at hour three. Four patients also had their lomustine deleted and replaced by etoposide 100 mg/m2 at hour four. Compared to earlier cycles of chemotherapy, there was a moderate increase in transfusion requirement (especially platelets) but the incidences of fever and neutropenia were unchanged. Glomerular function as measured by nuclear glomerular filtration rate (GFR) remained unchanged or improved at the end of therapy. The severity of nausea and vomiting after substitution was markedly improved. Four of the six patients are still in complete remission 19 to 41 months after diagnosis or recurrence. It is feasible to substitute carboplatin and etoposide into the '8 drugs in 1 day' regimen when extramedullary toxicity is found.