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Biomedical subjects

Lavjay Butani

Publications and source records attributed to Lavjay Butani.

34 records · Page 2Linked to original sources

Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil.

BACKGROUND: Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus. METHODS: Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F(2-alpha) and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids. RESULTS: Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1+/-3 vs. 6.0+/-1.1 ml/min in the nonsupplemented group; P<0.001); urinary PGF(2-alpha) excretion was also highest in the JO group (328+/-23 pg/mL, P<0.001 vs. the nonsupplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7+/-0.6% and 3.1+/-0.4%, respectively) and FO- (8.1+/-0.7% and 2.8+/-0.6%, respectively) treated animals. CONCLUSIONS: JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF(2-alpha) excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.

Animals↗

Life-threatening extrarenal lupus in children despite improvement in serologic findings.

Systemic lupus erythematosus (SLE) is an autoimmune disorder with the potential for multiorgan involvement. Serologic tests are helpful in establishing the diagnosis of SLE and predicting disease flares. However, there are few data on the relationship between the onset of new organ involvement and lupus serologies, especially in children. This report details our experience in managing two children with lupus nephritis. Both developed life-threatening extrarenal complications (cerebritis and carditis) soon after receiving high-dose immunosuppressive therapy and despite normalizing serologies. This lack of concordance between serologies and the development of carditis and cerebritis needs to be recognized so that health care professionals treating children with SLE can promptly intensify immunosuppressive medications and avoid life-threatening delays from seeking alternative explanations for symptomatology.

Adolescent↗

Validity of protein-osmolality versus protein-creatinine ratios in the estimation of quantitative proteinuria from random samples of urine in children.

BACKGROUND: Proteinuria is an important marker of kidney disease. Simple methods to determine the presence of proteinuria in a semiquantitative fashion require measurement of either a protein-creatinine or protein-osmolality ratio. METHODS: Urine samples from 134 healthy infants and children and 150 children from the pediatric nephrology practice were analyzed to develop normative data for protein-osmolality ratios on random urine samples and compare protein-osmolality with protein-creatinine ratio as a predictor of 24-hour urine protein excretion. Children were grouped according to age. Three groups were established: infants (<2 years), younger children (2 to 8 years), and older children (9 to 18 years). An adult cohort was similarly analyzed. RESULTS: For healthy children older than 2 years, the optimal value discriminating normal from abnormal protein excretion was determined to be a protein-osmolality ratio of 0.15 mg x kg H2O/mOsm. L; for children between 2 and 8 years old, 0.14; and for children older than 8 years, 0.17 (P = not significant between age groups). The corresponding optimal cutoff value for protein-creatinine ratio for the entire group of children older than 2 years is 0.20. Area under the curve analysis of receiver operator characteristic curves showed protein-creatinine ratio was superior to protein-osmolality ratio for predicting abnormal amounts of proteinuria in children and adolescents (P < 0.0001). In adults, both ratios are equally accurate. CONCLUSION: Given the superiority of protein-creatinine ratio in children, it would be appropriate to screen urine samples for proteinuria using protein-creatinine ratio rather than protein-osmolality ratio.

Adolescent↗

Pilot study describing the use of pravastatin in pediatric renal transplant recipients.

Renal transplant (Tx) recipients frequently develop hypercholesterolemia. Pravastatin (P) has been shown to be effective in adult renal Tx recipients, not only in reducing serum cholesterol, but possibly also in decreasing graft rejection. However, there are no data on the use of P in children following renal transplantation. We conducted a retrospective case-control study evaluating the safety and efficacy of P (10-20 mg/day) in reducing hypercholesterolemia, when used pre-emptively in the post-Tx period in seven children, compared with an historical control (C) group of nine children who had not received P. The two groups were comparable with respect to their demographics and in their pretransplant serum cholesterol. Compared with the C group, the mean serum cholesterol in the P group was lower at 3 months (159 mg/dL vs. 225 mg/dL), 6 months (134 mg/dL vs. 200 mg/dL), 9 months (134 mg/dL vs. 209 mg/dL), and 12 months (125 mg/dL vs. 195 mg/dL) (p < 0.005 for all, Student's two-tailed t-test). At 1 month only 43% of the P group had hypercholesterolemia compared with 67% of the controls; by 12 months this difference was even more significant (0% in the P group vs. 45% in the C group). None of the treated patients developed any adverse reactions. This study demonstrates that the pre-emptive use of P in pediatric renal Tx recipients appears to be effective in significantly reducing serum cholesterol. Whether this effect will translate into improved allograft and patient survival in the long term cannot be predicted at present and will require additional studies to evaluate.

Anticholesteremic Agents↗

End-stage renal disease after high-dose carboplatinum in preparation of autologous stem cell transplantation.

Stem cell transplantation is one therapy employed in the management of children with high-risk solid tumors. However, this therapy is not without risk, having been associated with multiple end-organ toxicities. Both acute renal failure and chronic renal insufficiency have been reported in marrow transplant recipients, primarily in the context of the use of calcineurin inhibitors and radiation therapy. This report reviews our experience in managing an adolescent with metastatic Ewing's sarcoma who developed rapid progression to end-stage renal disease following a pretransplant conditioning regimen with high-dose carboplatinum. She had not received radiation or prior cisplatinum therapy. The possible reasons for the patient's highly unusual course and recommendations on ways to prevent this complication are discussed.

Adolescent↗

Congenital acute myelogenous leukemia presenting as palpable renal masses in a neonate.

Our report concerns a neonate who was noted to have palpable kidneys soon after birth. Her clinical and radiologic findings were compatible with the diagnosis of autosomal recessive polycystic kidney disease. The patient eventually died of sepsis-related multiorgan failure, and on autopsy, surprisingly, was found to have leukemic infiltrates in the kidney. Healthcare providers need to be aware that congenital acute myelogenous leukemia, although rare, can present in the newborn period with nephromegaly.

Autopsy↗

Severe hyperphosphatemia resulting from high-dose liposomal amphotericin in a child with leukemia.

Children with acute lymphoblastic leukemia (ALL) are at risk for serious electrolyte abnormalities. The authors report their experience in managing a child with ALL who developed severe hyperphosphatemia as a consequence of a large exogenous load of phosphorus from high-dose liposomal amphotericin B. Health care providers need to recognize this potentially life-threatening complication of liposomal amphotericin B, since early detection and intervention can prevent significant morbidity.

Amphotericin B↗

Microhematuria after renal transplantation in children.

The renal transplant (Tx) recipient is at risk for developing various complications including urolithiasis, the only manifestation of which may be hematuria. However, there are no data on the prevalence of microscopic hematuria in renal Tx recipients. The objective of our study was to determine the prevalence of microhematuria in our pediatric Tx patients and to investigate the causes of microhematuria. Records of all pediatric renal Tx recipients followed at our center from September 1999 to September 2000 were retrospectively reviewed; of the 21 patients, seven (33%) had persistent microscopic hematuria that was first noted 2.9 years post-Tx. Patients with and without hematuria had similar baseline characteristics. Only one patient had pre-existing hematuria that continued post-Tx. The etiology of hematuria in the other six patients was: recurrent IgA nephropathy (one patient), CMV nephritis (one patient), and unexplained (four patients). None had renal calculi or hypercalciuria. Three of the four patients with unexplained hematuria have chronic allograft nephropathy, and the fourth (original disease dysplasia) has hypocomplementemia. At their last follow-up, 5.3 years after onset of hematuria, all patients are alive with stable allograft function. In conclusion, microscopic hematuria is not uncommon in pediatric renal Tx recipients. While causes of post-Tx hematuria are diverse, stones are not commonly seen. Whether chronic allograft nephropathy per se can be implicated as a cause of hematuria remains to be determined. Renal biopsies should be considered at the onset of hematuria if proteinuria and/or deterioration in renal function are seen concomitantly, to look for recurrent or de novo glomerulonephritis.

Adolescent↗

Early and late recipient graft function and donor outcome after laparoscopic vs open adult live donor nephrectomy for pediatric renal transplantation.

BACKGROUND: Laparoscopically procured live donor kidney grafts are increasingly transplanted into pediatric recipients. The safety and efficacy of this changed surgical practice are unknown. HYPOTHESIS: Outcomes of laparoscopic vs open donor grafts in recipients 18 years and younger are equivalent. DESIGN AND SETTING: Retrospective review at an academic tertiary care referral center. PATIENTS: Eleven consecutive pediatric recipients of laparoscopically procured kidneys between April 1, 1997, and December 31, 2001, were pair matched for age with 11 recipients of openly procured kidneys between December 1, 1991, and March 31, 1997; the 22 adult donors were also studied. MAIN OUTCOME MEASURES: Recipients: surgical complications, graft function and survival. Donors: perioperative morbidity and length of hospital stay. RESULTS: Twenty (91%) of 22 kidneys were donated by a parent of the recipient. In recipients of laparoscopically procured grafts, we observed significantly lower creatinine clearances and higher creatinine levels on days 1, 4, and 6, but by 1 month, graft function was similar in both groups. No significant differences in surgical complications, delayed function, acute and chronic rejection, and graft survival rates were found. No laparoscopic or open donor required blood transfusion, reoperation, or hospital readmission. One laparoscopic donor (9%) was converted to open nephrectomy. For laparoscopic vs open donors, median operative time was longer (difference, 67 min; P =.08), but median postoperative length of stay was significantly shorter (3 vs 5 days; P =.02). CONCLUSIONS: Laparoscopic live donor nephrectomy has no adverse impact on pediatric recipient outcomes. For donors, the laparoscopic operation is safe and the hospital stay is shortened. These results support the continued use of laparoscopically procured live donor kidneys in pediatric renal transplantation.

Adolescent↗

QTc interval in children with chronic renal failure and with renal transplants.

Prolongation of the QTc interval, a risk factor for cardiac arrhythmias, has been observed in adult hemodialysis patients; there are few data on the QTc interval in children with chronic renal failure (CRF) and following renal transplantation (Tx). The purpose of our study was to determine the QTc interval in children with CRF and post renal Tx. Twenty children with CRF and 16 children with renal Tx who were followed at the University of California, Davis, underwent prospective EKG monitoring. The mean QTc interval in the CRF and post-Tx cohorts was normal at 407.9 ms and 408.2 ms, respectively. None of the children with CRF had QTc prolongation. Two Tx recipients had QTc prolongation; both had cardiac dilatation on echocardiography (ECHO). There was no correlation between the QTc interval and the creatinine clearance in either group. However, a significant correlation was noted between QTc prolongation and cardiac dilatation on ECHO in the Tx group (P=0.02, Fisher's exact test). In conclusion, QTc prolongation is uncommon in children with CRF and following Tx, in the absence of cardiac dilatation. However, caution is still needed before prescribing medications known to cause QTc prolongation.

Adolescent↗

Corticosteroid-induced hypersensitivity reactions.

OBJECTIVE: To review and present data on the prevalence, clinical manifestations, diagnostic techniques, and management options in patients with hypersensitivity reactions to corticosteroid preparations. DATA SOURCES: All English language articles pertaining to human subjects were reviewed using the Pubmed database from 1964 to June 2002. Indexing terms used were anaphylaxis OR allergic OR anaphylactoid OR hypersensitivity AND steroid OR corticosteroid. Further cross-references were obtained after reviewing articles from the aforementioned search. STUDY SELECTION: A total of 11,493 articles were identified with the above search terms. Only those articles, including letters and editorials, describing systemic reactions to steroids were included in the review. Excluded from our review were articles dealing with contact dermatitis to topical steroid preparations. This resulted in a total of 80 articles which were reviewed. RESULTS: Although rare, steroid-induced hypersensitivity reactions do occur. They range from minor rashes to the more serious cardiovascular collapse. The mechanisms of steroid-induced adverse events vary from patient to patient, some being classic immunoglobulin E-mediated whereas others are pseudoallergic in nature. Skin testing and provocative challenges offer two ways to diagnose such reactions. Treatment consists of substituting the steroid with an alternative preparation which can be tolerated by the patient. CONCLUSIONS: Although little is known about the epidemiology of steroid-induced hypersensitivity, because most data are derived from case reports, it is clear that steroid-induced hypersensitivity is a heterogeneous entity, with no single uniform mechanism. A great deal of work still needs to be done so that the pathogenesis of such adverse events can be clearly determined and effective therapeutic interventions devised.

Adrenal Cortex Hormones↗

Ureterocystoplasty (bladder augmentation) with a solitary kidney.

Children who develop end-stage renal disease (ESRD) as a result of obstructive uropathies require evaluation and treatment of associated bladder dysfunction to ensure a good outcome following renal transplantation. Bladder dynamics can often be optimized medically, although surgical intervention is occasionally necessary. For those patients who require bladder augmentation, the use of a dilated native ureter (ureterocystoplasty) is preferred to the more commonly used intestine or stomach (enterocystoplasty), which carry a higher risk of complications. Unfortunately, most patients do not have a suitable anatomy for ureterocystoplasty and, by necessity, intestine or stomach has to be utilized. Herein, we describe the successful application of ureterocystoplasty in the presence of ESRD and a solitary kidney prior to renal transplantation. We believe that owing to the many advantages of native urothelium, every effort should be made to use ureter and avoid the use of intestine.

Child, Preschool↗