Assessing glomerular filtration rate in healthy Indian adults: a comparison of various prediction equations

BACKGROUND: Accurate measurement of renal function is important for the diagnosis, stratification and management of kidney disease. As the use of recommended filtration markers is limited by cumbersome and costly techniques, renal function is typically estimated by using various specifically derived prediction equations. Most of these equations have been derived from Caucasian patients suffering from varying degrees of chronic kidney disease. This study considers the validity of these equations in an Indian population without known kidney disease. METHODS: One hundred and twenty-two consecutive renal donors who had undergone 99mTc-diethylenetriaminepentaaceticacid (DTPA) glomerular filtration rate (GFR) estimation were enrolled. The predictive capabilities of the Cockcroft and Gault equation for creatinine clearance corrected for body surface area (CG-CrCl), CG-CrCl corrected for GFR (CG-GFR), modification of diet in renal disease (MDRD) 1, MDRD 2 and 24-hr urinary creatinine clearance (urine-CrCl) were evaluated with DTPA GFR as measured GFR. RESULTS: The mean age of the study population was 44.7 yrs with 72.2% being female). The mean measured DTPA GFR was 83.42 ml/min with a range of 61-130 ml/min. The median % absolute difference between the calculated and measured GFR was 19.7, 15.4, 19.3, 20.8 and 25.5, respectively, for CG-CrCl, CG-GFR, MDRD 1, MDRD 2 and urine-CrCl. Pearson's correlation between the measured and estimated GFR varied from 0.09-0.27. The precision as reflected by R2 value was 0.05 for CG-CrCl and CG-GFR, 0.06 for MDRD 1 and MDRD 2 and 0.01 for urine-CrCl. The bias was -14.14, 1.46, 11.89, 17.70 and -2.80 for CG-CrCl, CG-GFR, MDRD 1, MDRD 2 and urine-CrCl, respectively. The accuracy within 30% was 71.3, 85, 86, 76 and 69% for CG-CrCl, CG-GFR, MDRD 1, MDRD 2 and urine-CrCl, respectively. CONCLUSIONS: Our results from a healthy Indian population suggest that of all the predictive equations, MDRD 1 and MDRD 2 were the most precise, MDRD 1 the most accurate and CG-GFR the least biased. However, the poor correlation and error level exhibited by these equations makes them sub-optimal for clinical use.     

Cell nanosurgery using ultrashort (femtosecond) laser pulses: applications to membrane surgery and cell isolation

Membrane surgery and nanosurgical cell isolation using high-intensity femtosecond laser pulses is reported. We demonstrate the applicability of using ultrashort (femtosecond) laser pulses for performing surgery on live mammalian cells. When sub-10 femtosecond pulses were focused onto the cell, precise sub-micron surgical cuts were made on the biological membrane. Traversing the cells relative to the focused laser spot, we report on localized nanosurgical ablation of focal adhesion adjoining epithelial cells. In each study, the surgery was conducted without morphologically compromising the cells.     

Fibrillary Glomerulonephritis Presenting as Rapidly Progressive Renal Failure in a Young Female: A Case Report

Fibrillary Glomerulonephritis (FGN) is a rare clinical entity presenting in majority of patients with nephrotic range proteinuria, microscopic hematuria, impaired renal function and hypertension. The mean age of presentation is reported to be beyond 50 years with 50 patients developing end stage renal disease within a few years. A 28-year-old female presented to us with non-nephrotic range proteinuria, rapidly progressive renal failure (RPRF), microscopic hematuria and mild hypertension. The patient had undergone a renal biopsy at a peripheral center, which was reported as membranoproliferative glomerulonephritis (MPGN) and was being treated with steroids without any benefit. The patient on re-biopsy at our center was diagnosed as FGN on electron microscopy (EM). The patient responded to intravenous pulse methylprednislone and oral cyclophosphamide and is off dialysis for 10 months now. This case highlights the varied clinical and histological presentations of FGN which makes the disease difficult to diagnose more so, in a country like ours where EM is available in only a few centers. An accurate diagnosis aided by high index of clinical suspicion and EM can help in the initiation of appropriate therapy, thereby improving the outcome in this disease which otherwise has a poor prognosis.     

Phagocytic polymorphonuclear function in patients with progressive uremia and the effect of acute hemodialysis

BACKGROUND: Susceptibility to infections is a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Polymorphonuclear leukocytes (PMNs) play a major role in the host defense against various infections. Although the phagocytic function of PMNs in uremic patients has been subjected to repeated evaluation, results have been inconsistent. Also, the effects of progressive uremia and acute hemodialysis (HD) on polymorphonuclear function have been scarcely evaluated. METHODS: In this study, we assessed the phagocytic index (PI) of PMNs following their uptake of IgG-coated sheep erythrocytes in patients with varying severity of CKD and in healthy controls. In patients with advanced renal failure, the effects of acute HD on PI pre- and post-HD were also studied. RESULTS: A total of 30 patients with CKD and 15 healthy controls were studied. Patients with CKD were categorized into two groups: mild to moderate renal failure (S. Creatinine 2-6 mg/dL) and advanced renal failure (S. Creatinine >6 mg/dL) (n=15 for each). All three groups were age and sex matched. Patients with advanced renal failure had significantly impaired PI (4.03 +/- 1.15) as compared to patients with mild to moderate renal failure (7.17 +/- 2.62) and normal controls (8.13 +/- 3.31) (p < 0.001 for both). There was a statistically insignificant decline in the PI in patients with mild to moderate RF when compared to controls (7.17 +/- 2.62 versus 8.13 +/- 3.31). In patients with advanced renal failure, acute HD led to a significant improvement in PI (5.52 +/- 1.55 versus 4.03 +/- 1.15, p < 0.01). CONCLUSION: In patients with CKD, there is a progressive decline in the phagocytic index of the PMNs with increasing severity of uremia. Significant improvement in the phagocytic index following acute hemodialysis suggests the role of a circulating uremic toxin in this PMN dysfunction.     

Iris intraocular foreign bodies: safe and successful removal through limbus

Metallic iris intra ocular foreign body (IOFBs) with minimal ocular damage pose an interventional challenge. We report safe removal of metallic intraocular foreign bodies embedded on the iris, in three cases by use of intraocular magnets. Two eyes had a clear lens with best corrected visual acuity (BCVA) of 20/20, while the third eye had a BCVA of 20/200 with siderotic cataract. Ultrasound biomicroscopy confirmed the superficial impaction of IOFB into the iris. Foreign bodies were successfully removed via the limbal route with a 20 g intravitreal magnet atraumatically in all 3 cases with preservation of their pre-operative BCVA. Case series highlights the usefulness and safety of intraocular magnet for removal of metallic iris foreign bodies in selected cases. Prior ultrasound biomicroscopy to know the actual depth of penetration of IOFB into the iris and preoperative confirmation of magnetic property of IOFB are essential.     

Giant epidermoid cyst as an unusual presentation of hypoglobus and ptosis

A 24-year-old man presented with a large right frontal epidural epidermoid cyst that resulted in right hypoglobus and right upper eyelid ptosis. CT and MRI revealed a bone-destroying mass involving the right frontal bone and eroding through the right orbital roof. Complete surgical removal was performed through a frontal craniotomy. After surgery, there was near-complete resolution of the hypoglobus and ptosis.     

Evaluation of fluid absorption during holmium laser enucleation of prostate by breath ethanol technique

PURPOSE: In a prospective manner we studied various factors affecting fluid absorption during HoLEP. We also simultaneously evaluated changes in serum electrolytes and hemoglobin decrease during HoLEP. MATERIALS AND METHODS: This prospective study comprised of 53 patients who underwent HoLEP at our institute. Irrigation fluid was normal saline tagged with ethanol (1% w/v). Intraoperatively a standard breath analyzer was used to monitor expired breath ethanol levels during the procedure at 10-minute intervals. Patients who absorbed irrigating fluid as indicated by positive intraoperative breath tests were considered absorbers. Serum electrolyte and hemoglobin estimations were done before and after surgery. Total irrigation time, amount of irrigation fluid used, weight of resected tissue and presence of capsular perforation were recorded. Statistical analysis was performed to observe the effects of various factors on the amount of intraoperative fluid absorption. RESULTS: Of 53 patients studied 14 (26.41%) demonstrated fluid absorption in the range of 213 to 930 ml (mean 459). Preoperative prostate weight, total irrigation time, amount of irrigation fluid used and resected tissue weight were all significantly greater in absorbers. Similarly, absorbers had a statistically significant decrease in hemoglobin level postoperatively. There was no statistically significant change in serum electrolytes between absorbers and nonabsorbers. CONCLUSIONS: Preoperative weight of prostate, total irrigation time, amount of irrigation fluid used and weight of resected tissue all directly influence the amount of fluid absorption during HoLEP. There is no significant change in serum electrolytes and no risk of the transurethral resection syndrome.     

Neutropenia and febrile neutropenia in patients with Hodgkin's lymphoma treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy

When uncomplicated neutropenia during doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy for the treatment of Hodgkin's lymphoma is encountered, it is unclear whether or not treatment should be modified. In the present study, we determined the incidence of neutropenia, febrile neutropenia, and the relationship of febrile neutropenia to grade III/IV neutropenia and dose modification, in a large university patient population. We reviewed the charts of patients diagnosed with Hodgkin's lymphoma between 1 January 1990 and 31 December 2002 who were treated with ABVD chemotherapy, and seen at the University of Iowa with complete diagnosis, staging, and treatment dosing records. Adequate data was available on 894 treatments in 81 patients with Hodgkin's lymphoma treated with ABVD chemotherapy. Grade III/IV neutropenia was present on the scheduled day of treatment in 187 (20.9%) treatments in 64 (79%) patients. Grade III/IV neutropenia was most common at cycle 1 day 15. Febrile neutropenia developed nine times in eight patients, and eight episodes of febrile neutropenia developed when the treatment-day absolute neutrophil count (ANC) > or =1000. Dose delay of >4 days and/or dose reduction to <80% of original doxorubicin dose following grade III/IV neutropenia occurred in 29 of 187 treatments, with no episodes of febrile neutropenia. With grade III/IV neutropenia on the day of therapy, 158 treatments were administered without dose reduction or dose delay with one subsequent episode of febrile neutropenia. Neutropenia during ABVD is common, and dose modification for uncomplicated neutropenia on the day of treatment may not reduce the risk of febrile neutropenia. It may be possible to maintain dose intensity in the face of uncomplicated neutropenia during ABVD therapy.     

Effect of von Willebrand Factor on the Pharmacokinetics of Recombinant Human Platelet Glycoprotein Ibα-Immunoglobulin G1 Chimeric Proteins

Purpose Recombinant human platelet glycoprotein Ibα-immunoglobulin G1 chimeric proteins (GPIbα-Ig) have varying levels of anti-thrombotic activities based on their ability to compete for platelet mediated adhesion to von Willebrand Factor (vWF). Valine substituted GPIbα-Ig chimeras, at certain position, increase the binding affinity to vWF over its “wild-type” GPIbα-Ig analog. The purpose of this study was to determine the pharmacokinetics of two valine substituted GPIbα-Ig chimeras, GPIbα-Ig/1V (valine substitution at 239 position) and GPIbα-Ig/2V (double valine substitution at 233 and 239 position), in mice, rats and dogs.Methods Head-to-head comparisons of pharmacokinetics of GPIbα-Ig/1V and GPIbα-Ig/2V were investigated in rats and dogs after intravenous administration. Since vWF precipitates in the serum but not in plasma preparation, the concentration-time profiles of GPIbα-Ig/2V in rats were examined from the same blood samples for determination of matrix effect. The disposition of GPIbα-Ig/2V was also compared in vWF-deficient versus wild-type mice.Results For GPIbα-Ig/2V, the serum clearances were 2.62 ± 0.27 ml/hr/kg in rats and 1.97 ± 0.24 ml/hr/kg in dogs. The serum clearances of less potent GPIbα-Ig/1V were 1.08 ± 0.08 and 0.97 ± 0.19 ml/hr/kg in rats and dogs, respectively. In addition, the serum clearance of GPIbα-Ig/2V of 1.53 ml/hr/kg in vWF-deficient mice was lower than that in wild-type mice of 2.79 ml/hr/kg.Conclusion The difference in disposition for valine substituted forms of GPIbα-Ig in laboratory animals are likely affected by their enhanced binding affinity for circulating vWF.