S.C. Tiwari

Prospective randomized control trial of isoniazid chemoprophylaxis during renal replacement therapy

Abstract: Background. Infectious diseases remain among the major morbid events in patients with end‐stage renal disease (ESRD) on renal replacement therapy (RRT). In developing countries, tuberculosis (TB) has been found to occur more frequently in these patients than in the general population. Efficacy of isoniazid (INH) chemoprophylaxis has been seen in other situations, such as human immunodeficiency virus infection. However, studies on INH prophylaxis in ESRD patients on RRT are limited.

Treatment of Acute Rejection in Live Related Renal Allograft Recipients: A Comparison of Three Different Protocols

We present our experience on the comparison of three different modes of steroid therapy, oral prednisolone (OP), intravenous dexamethasone (IVDX) and intravenous methylprednisolone (IVMP) in the treatment of acute rejection (AR) in renal allograft recipients. Between January 1980 and January 1992, 206 patients underwent live related renal transplantation. Before 1990, all received prednisolone (PRED) and azathioprine (AZA) only. After 1990, patients were given PRED, AZA and cyclosporine (CsA). After 1 year, CsA was stopped and patients were converted to a two-drug regimen only. Of the 206 patients, 180 (87.4%) were male and mean age was 30.3+/-8.7 years (range 14-63). During the mean follow-up of 43.5 months, 178 episodes of AR were seen in 121 patients. Each episode was considered as a separate entrant in the study. Conventional immunosuppression was given in 151 episodes and 27 episodes were on triple-drug therapy. Diagnosis of AR was made by clinical, sonography, nuclear scan with or without graft biopsy evidence. Of the 178 AR, 110 (61.8%) were within 3 months, 36 (20.2%) were between 3 months and 1 year and 32 (18%) were after 1 year. OP was given in 11 cases while IVDX and IVMP were given in 48 and 119 cases respectively. Overall, 154 (86%) showed either a complete or partial response to antirejection therapy. Response to therapy was 91, 90 and 85% in OP, IVDX and IVMP groups respectively. There was no statistical difference in response rate in different groups. There was also no difference in side effects in three different groups. Our data suggest that it is the high dose of steroid rather than mode of therapy which is responsible for therapeutic benefit in treatment of AR.

Generic tacrolimus (Pan Graf) in renal transplantation: an experience of 155 recipients in India.

BACKGROUND The safety and efficacy of tacrolimus in transplantation are well established. However, tacrolimus (Pan Graf) has only been available in India for the last 2 years. We conducted this study to assess the safety and efficacy of tacrolimus in living related kidney transplantation. Herein we have reported our experience with tacrolimus as de novo therapy in a living related renal transplant program. MATERIALS AND METHODS One hundred fifty-five consecutive recipients of living donor renal allografts were included in this study after consent and ethical clearance. Immunosuppression consisted of tacrolimus, mycophenolate mofetil or azathioprine, and steroids. The dose of tacrolimus was adjusted according to levels done on a regular basis. All patients were followed for periods ranging from 3 to 33 months. All episodes of graft dysfunction were evaluated by a graft biopsy. We evaluated the effects of this regimen on the incidence of graft rejection, graft survival, patient survival, and new onset diabetes mellitus. Six patients were diabetic prior to transplantation and 9 patients were hepatitis C virus (HCV) positive. RESULTS There were 137 male and 18 female patients. The incidence of acute rejection was 3.87%; 17.93% developed new onset diabetes mellitus; and 77.7% of HCV-positive patients and 14.07% of HCV-negative patients developed posttransplantation diabetes mellitus. The patient survival at the current follow-up was 94.19%. CONCLUSION This generic form of tacrolimus is a safe, effective immunosuppressant in living related renal transplantation.

Fibrosing cholestatic hepatitis in renal transplant recipient with CMV infection: A case report

Fibrosing cholestatic hepatitis (FCH) is an uncommon complication of renal transplantation. It is usually associated with hepatitis B and C viral infection. It is further rare in renal transplantation in absence of HBV and HCV infection. To the best of our knowledge, only three cases of FCH in renal transplantation, which were both HBV and HCV negative, have been reported to date. Out of these, two cases were diagnosed to have CMV infection and the third was attributed to azathioprin. We are presenting another case of FCH in a renal transplant recipient with CMV infection.

Fungal panniculitis in renal transplant recipients

Abstract: Panniculitis may result due to various etiologies. In post‐transplant immunosuppressed patients infection is the foremost cause of panniculitis. We present 2 cases of fungal panniculitis in renal transplant recipients. The first patient presented with non‐tender firm erythematous plaques on the left thigh. Biopsy showed panniculitis with cryptococci. Subsequent investigations revealed the presence of cryptococcal antigens in the blood, urine, and bronchoalveolar lavage fluid. There was no evidence of cryptococcal meningitis. The second patient complained of subcutaneous nodules on the trunk and right thigh. Biopsy of one of the nodules showed panniculitis with histoplasma. This patient had been treated earlier (inadequately) for disseminated histoplasmosis. Both the cases responded well to conventional amphotericin B therapy. Their renal functions remained stable.

Spectrum of acute renal failure and factors predicting its outcome in an intensive care unit in India.

Identification of factors causing acute renal failure (ARF) and its associated poor prognosis in critically ill patients can help in planning strategies to prevent ARF and to prioritize the utilization of sparse and expensive therapeutic modalities. Most of the studies in such patients have been done in the developed world, and similar data from the developing world is sparse. We analyzed 45 consecutive patients who developed ARF in the intensive care unit (ICU) during a 12-month period. Demographic and detailed biochemical profile, previous chronic illness, precipitating factors, number of failed organs, type of ARF (oliguric/nonoliguric), and need for and type of renal replacement therapy (RRT) received were recorded at the time of admission to ICU and during the course of illness. The mean age of these patients was 43.1 years, with 75.6% being males. Hypotension, sepsis, and use of nephrotoxic drugs were common precipitating factors for ARF in these patients. However, multiple precipitating factors were present in the majority (80%): 81.5% had at least one organ failure prior to development of ARF, 71.1% had oliguria, and 71.1% required RRT. Intermittent hemodialysis was the most common form of RRT given. Patient mortality was 64.4%, with 15 of the 16 surviving patients becoming dialysis independent. We observed an increase in mortality from 0% to 100%, depending on the number of failed organs from one to six. On comparing the predictor outcomes between survivors and nonsurvivors by multivariate analysis, only the number of failed organs at the time of ARF (2.6 ± 0.9 vs. 4.5 ± 0.8) and serum albumin <3.0 g/dL were found to be statistically significant. To conclude, ARF in critically ill patients is multifactorial in origin and carries a high mortality. Mortality in these patients increases with increasing numbers of failed organs and with a serum albumin of <3.0 g/dL.

Reduced CR1 Expression on Erythrocytes of Idiopathic Focal-Segmental Glomerulosclerosis Patients

This article is also accessible online at: http://BioMedNet.com/karger Dear Sir, Focal-segmental glomerulosclerosis (FSGS) is characterized by sclerosis and hyalinosis of some, but not all, glomeruli (hence the term focal). Enlargement of the less affected glomeruli is the characteristic of the idiopathic form. Idiopathic nephrotic syndrome is more common in adults, particularly between the ages of 16 and 30, and comprises up to 20% of all nephropathies in adults [1]. Cause and pathogenesis of focal sclerosis are unknown. FSGS is also characterized by non-involvement of immune complexes (ICs) in the pathogenesis, but several clinical and laboratory findings have been proposed suggesting that FSGS is an immune system mediated disorder [2, 3]. Some investigators have demonstrated that abnormalities of the lymphocyte function in minimal-change nephrotic syndrome are also present in FSGS [4, 5]. The involvement of serum in improving the status of disease was supported by a report indicating the role of C3, the third component of complement, as a cofactor in antigen-dependent T cell activation [6]. The protective role of complement entails the binding of C3b, a split product of C3, to ICs which facilitates their uptake through complement receptors on phagocytic cells [7]. The receptor for C3b, CR1, on erythrocytes has attracted increasing attention because of its role in a physiologic immune defence mechanism [8–10]. Since erythrocytes by far outnumber the other blood corpuscles with CR1 [11], they are able to act as a primary scavenger for disposing ICs in the circulation, preventing them from depositing in vessels and glomeruli. The role of CR1 in the pathogenesis of FSGS is not known, and to evaluate whether CR1 expression is altered in FSGS patients, the present study was undertaken. We have investigated the expression of CR1 on the erythrocytes of 10 patients with nephrotic syndrome and biopsy-proven FSGS with no ICs deposition as compared with erythrocyte CR1 expression of normal individuals using flow cytometry. Blood samples were taken prior to the steroid therapy. The proteinuria of the patients was in the nephrotic range (3.0–12.0 g/day) with a mean of 6.2 g/day. The serum creatinine levels were in the range of 0.9–2.7. Quantitation of CR1 levels using monoclonal anti-human CR1 and fluorescein isothiocyanate labelled antimouse IgG

Urinary Sporotrichosis in a Renal Allograft Recipient

Dr. Sanjay K. Agarwal, Assistant Professor, Department of Nephrology, Aiims, New Delhi-110029 (India) Dear Sir, We are reporting a case of urinary sporotrichosis in a renal transplant recipient. The patient had a radiolucent calculus with recurrent urinary tract infection. A 23-year-old male, having chronic glo-merulonephritis with end-stage renal failure underwent renal transplantation in July 1985. His mother was the donor with one haplotype match with the recipient. Postoperatively his renal function did not improve steadily. Ultrasound examination of the abdomen showed moderate hydronephrosis of the graft with narrowing of the lower end of the ureter. After confirming the finding on radionucleid scan on the 7th postoperative day, he was reoperated and a ureteroneocystostomy was done. Postoperatively he developed supra-pubic urinary leak which was managed conservatively. Following surgery his renal function improved slowly and on the 17th postoperative day serum creatinine was 106 μmol/l (1.2 mg/dl). He continued to have recurrent urinary tract infections which were treated according to the urine culture and sensitivity. On the 75th day following transplantation, a follow-up ureterocystoscopy was done which was essentially normal. However, his symptoms of lower urinary tract infection continued to persist even though the urinary cultures were repeatedly normal. In April 1986, although a plain radiogram of the abdomen was normal, the patient passed a stone per urethra, which was mainly made of ammonium phosphate with traces of calcium and oxalate. Keeping the possibility of a radiolucent calculus he was admitted for investigations. While in the hospital, he had acute retention of urine associated with enlargement of the graft which spontaneously got relieved within 12 h. However, a repeat ultrasonogram still showed hydroureterone-phrosis of the allograft with an echoic shadow at the lower end of the ureter. An antegrade pyelography performed at this time showed a dilated ureter (1.2 cm) and a stone at the lower end of the ureter. As the stone could not be dislodged, a percutaneus nephrostomy was done. Once the acute stage was over, he was operated for ureterolithotomy. During surgery multiple small yellowish calculi were found at the lower end of the ureter with a large stone 2 cm proximal to the vesicour-eteric junction

Diagnosis of glomerular haematuria by imagecytometry of urinary red cells.

Accessible online at: www.karger.com/journals/nef Dear Sir, Haematuria is an important and common problem in clinical practice. It may be caused by urological problems or ailments related to nephrology such as glomerulonephritis. Early detection of haematuria and differentiation between glomerular and nonglomerular type is essential for determination of the correct line of investigation and treatment [1, 2]. Glomerular haematuria is associated with a marked variation in size and shape of red cells, frequently with loss of hemoglobin, leading to many ‘dysmorphic’ cell populations. Nonglomerular haematuria is accompanied by a uniform morphology with less hemoglobin loss leading to ‘isomorphic’ cell populations [1–3]. Phase contrast microscopy of red blood cells (RBCs) in urine is the standard practice for diagnosis of haematuria, but the method is subjective, less accurate and the criteria are variable [2]. Recently automated urine flowcytometer is being used for diagnosis of origin of haematuria where the size of the red cells is determined by estimating the forward scatter (FSC) intensity of the cells without taking into account the variation in their shape and hemoglobin content [4]. We have undertaken a study to evaluate the urine red cells with the help of an automated computerized image analysis system [5] for determination of (1) size (area, area equivalent diameter and perimeter), (2) variation in shape in the form of form factor and (3) hemoglobin content by integrated optical density (IOD). An unstained coverslip preparation [2] of mid-stream fresh second morning urine samples were subjected to image analysis [5, 6] from 86 patients in this study with 52 males and 34 females, age ranging from 5 to 68 years (mean 36 B 21). In all these cases the sites of origin of red cells were confirmed later with clinical, radiological and biochemical investigations [2]. Forty-six patients had glomerular haematuria with different types of glomerulonephritis and 40 patients had nonglomerular causes like cancers and stone diseases. The glomerular RBCs were significantly smaller in diameter, area and perimeter than nonglomerular RBCs with a greater variation in shape and lower IOD (p ! 0.0001 to ! 0.0002) (table 1). Taking the 95 percentile value (5.3 Ìm) as cut-off value of red cell diameter, 93% of cases of glomerular haematuria could be diagnosed correctly, similarly 93, 92, 90 and 95% of cases could be diagnosed by cut-off values of 33.6 Ì2 for area, 19.1 Ìm for perimeter, 0.5 for form factor and 0.035 for IOD, respectively. With multiparametric analysis with cut-off values of all Table 1. The range and mean (BSD) of different parameters in glomerular (I) and nonglomerular (II) haematuria

Clinical Profile and Course and Outcome of Late Acute Rejection Episodes in Living-Related-Donor Renal Allograft Recipients

We prospectively monitored clinical data and renal function at monthly intervals in 165 patients who had received living-related-donor renal allografts in our institution between January 1981 and December 1991 and had a functioning allograft for 1 year or longer. During a mean follow-up period of 47.2 (range 13-155) months, 32 patients (17.2%) developed late acute rejections, of which 14 (43.7%) were asymptomatic. Amongst the symptomatic late acute rejections, worsening of hypertension was the commonest finding, being present in 11 (61.1%) patients, followed by oliguria in 8 (44.4%) and weight gain in 7 (38.8%) patients. Of these 32 late acute rejections, as many as 28 (87.5%) showed a response to antirejection therapy with high-dose steroids: 5 (15.6%) a complete response and 23 (71.9%) a partial response. The response rate was 100% if it was the first acute rejection (20% complete and 80% partial), 78.6% if it was the second (14.3% complete and 64.3% partial), and no or only a partial response to treatment if it was the third acute rejection episode. On long-term follow-up, patients who had responded to to antirejection treatment had a significantly better graft survival as compared with nonresponding patients: 76 and 27%, respectively. Our observations suggest that routine monitoring of the renal function at frequent intervals is essential for early diagnosis and treatment of acute rejections, even during the late posttransplant period. The chances of a response to antirejection therapy are higher during the first episode of late acute transplant rejection as compared with second or a third late rejection event.