Bone marrow cells contribute to tubular epithelium regeneration following acute kidney injury induced by mercuric chloride.

BACKGROUND & OBJECTIVES: Acute tubular necrosis (ATN) caused by renal ischaemia, renal hypo-perfusion, or nephrotoxic substances is the most common form of acute kidney injury (AKI). There are a few treatment options for this life-threatening disease and the mortality rate exceeds 50 per cent. In critical cases of AKI the only option is renal transplantation. In the present study we evaluated whether bone marrow cells (BMCs) are involved in regeneration of kidney tubules following acute tubular necrosis in the mouse. METHODS: Six to eight week old C57BL6/J and congenic enhanced green fluorescence protein (eGFP) mice were used. The relative contributions of eGFP-expressing BMCs were compared in two different approaches to kidney regeneration in the mercuric chloride (HgCl 2 )-induced mouse model of AKI: induced engraftment and forced engraftment. In vitro differentiation of lineage-depleted (Lin - ) BMCs into renal epithelial cells was also studied. RESULTS: In the forced engraftment approach, BMCs were found to play a role in the regeneration of tubules of renal cortex and outer medulla regions. About 70 per cent of donor-derived cells expressed megalin. In vitro culture revealed that Lin - BMCs differentiated into megalin, E-cadherin and cytokeratin-19 (CK-19) expressing renal epithelial cells. INTERPRETATION & CONCLUSIONS: The present results demonstrate that Lin - BMCs may contribute in the regeneration of renal tubular epithelium of HgCl 2 -induced AKI. This study may also suggest a potential role of BMCs in treating AKI.

Epididymal abscess in renal transplant: uncommon presentation of Klebsiella septicemia.

We present a renal allograft recipient 16 months posttransplant with an unusual infectious complication. This gentleman was antihepatitis C virus pretransplant, had a live unrelated transplant, and was taking cyclosporine, mycophenolate mofetil, and prednisolone. He developed diabetes and left scrotal abscess 3 months posttransplant and underwent left orchiectomy. He developed acute right epididymitis progressing to epididymal abscess, septicemia, and acute chronic graft dysfunction. Blood cultures and aspirated pus cultures grew Klebsiella pneumoniae and were treated with intravenous antibiotics, to which he responded. This case highlights an unusual complication in renal transplant and its successful management.

Detection of Cryptococcus by conventional, serological and molecular methods.

The rising incidence of cryptococcosis in India is posing a serious threat. Due to lack of sensitive methods for diagnosis, high morbidity and mortality are associated with the disease. Early diagnosis is essential to prevent serious complications. Therefore, we attempted to find highly sensitive and specific detection methods. A comparative evaluation of the detection of cryptococcosis was done by conventional (direct microscopy and culture) and rapid diagnostic [latex agglutination test (LAT), enzyme immunoassay (EIA) and PCR] methods. The study was done on 359 samples from 52 positive patients and 30 negative controls in an Indian set-up. Evaluation was done for cerebrospinal fluid (CSF), serum and urine separately. The diagnostic value of the tests was assessed in pre-treatment samples, and follow-up tests were also done on samples obtained after initiation of treatment. PCR had the highest sensitivity, followed by EIA and LAT, both before and after treatment. The positive detection by LAT, EIA and PCR was the longest in CSF (>90 days), followed by serum ( approximately 65 days) then urine ( approximately 45 days) after initiation of treatment. Our results indicated that the sensitivity and specificity of PCR and EIA were comparable in urine, CSF and serum for diagnosis of cryptococcosis.

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.

Assessing suitability for renal donation: can equations predicting glomerular filtration rate substitute for a reference method in the Indian population?

BACKGROUND: Accurate measurement of donor renal function has important long-term implications for both the donor and recipient. As the use of recommended filtration markers is limited by cumbersome and costly techniques, renal function is typically estimated using 24-hour urinary creatinine clearance (urine-CrCl). Prediction equations used for rapid bedside estimation of glomerular filtration rate (GFR) are simple and overcome the inaccuracies of urinary collection and, if validated, can expedite the donor workup besides reducing the cost. We assessed the suitability of urine-CrCl and prediction equations for evaluating potential Indian renal donors. METHODS: 173 consecutive renal donors were enrolled. The predictive capabilities of the Cockcroft and Gault equation for creatinine clearance (CrCl) corrected for body surface area (CG-CrCl), CG-CrCl corrected for GFR (CG-GFR), MDRD-1, MDRD-2 and urine-CrCl were evaluated with 99mTc-diethylenetriaminepentaacetic acid (DTPA)-GFR as reference GFR. RESULTS: The study population had a mean age of 44.1 years with 74% being females. Mean DTPA-GFR was 83.85 ml/min/1.73 m2. The median percent absolute difference was most with urine-CrCl and least with CG-GFR (21.84 and 13.82). The Pearson's correlation varied from 0.08 to 0.26 (urine-CrCl and MDRD-1). The precision was most with MDRD-1 and least with urine-CrCl (0.07 and 0.01). The bias was least with CG-GFR and most with MDRD-2 (1.34 and 17.16). The number of subjects with predicted GFR values within 30% of DTPA was most with MDRD-1 (86%) and least with urine-CrCl (69%). The sensitivity for selecting a donor with a GFR of > or = 80/ml/min/1.73 m2 was the most with CG-GFR (65.7%), while specificity was maximum with MDRD-2 (90.1%). CONCLUSION: Our results in potential Indian renal donors show that of all the prediction equations MDRD-1 is the most precise and accurate, while CG-GFR is the least biased. However, the poor correlation and level of error exhibited by these equations makes them suboptimal for donor evaluation.

Effect of local mupirocin application on exit-site infection and peritonitis in an Indian peritoneal dialysis population.

BACKGROUND: Staphylococcus aureus-associated peritonitis and catheter exit-site infections (ESIs) are important causes of hospitalization and catheter loss in patients undergoing chronic peritoneal dialysis. Intranasal and topical use of mupirocin has been found to be an effective strategy in decreasing S. aureus-related infectious complications in persons who are carriers of S. aureus; however, there is no consensus regarding the prophylactic use of mupirocin irrespective of carrier status. We aimed to determine the potential effectiveness of application of mupirocin cream at the catheter exit site in preventing ESI and peritonitis irrespective of carrier status in a tropical country such as India. METHODS: This prospective historically controlled study was done in a total of 40 patients. From August 2003, all patients, incident and prevalent, were instructed to apply 2% mupirocin cream daily to the exit site instead of the older practice of povidone-iodine and gauze dressing. Patients were not screened to determine whether they were S. aureus carriers. The infection-related data for 1 year, until July 2004, were compared with the historical control, which was infection-related data for the year preceding the year of mupirocin application. RESULTS: Mean age of the study population was 62 years, with 61.8% being male and 64.3% being diabetic. Local application of mupirocin led to a significant reduction in the incidence density per patient-month of both ESI and peritonitis compared to controls (0.15 vs 0.37 and 0.37 vs 0.67, p = 0.01 for both). This amounted to a relative reduction of 60.5% and 55% respectively. ESI and peritonitis due to S. aureus were also significantly lower in the study group compared to controls (incidence density per patient-month 0.05 vs 0.13 and zero vs 0.17 respectively, p < 0.01 for both). There occurred no catheter removal due to infection-related complications during the study period compared to two during the control period. None of the patients reported a mupirocin-related adverse effect. CONCLUSIONS: Daily application of mupirocin at the exit site is a well-tolerated and effective strategy in reducing the incidence of ESI and peritonitis in a tropical country such as India. It can thus significantly reduce morbidity, catheter loss, and transfer to hemodialysis in peritoneal dialysis patients.

Factors affecting the use of peritoneal dialysis among the ESRD population in India: a single-center study.

OBJECTIVES: Factors such as limited health-care budget allotment and poor accessibility of the majority of the population to hemodialysis (HD) facilities should favor the use of peritoneal dialysis (PD) in India. However, only 6% of end-stage renal disease patients undergoing dialysis in India are on PD. We undertook this prospective study to evaluate various factors that could contribute to this low rate of use of PD at a tertiary-care state-run hospital in Northern India. METHODS: All the patients who entered our HD or PD program from August 2001 to December 2003 were interviewed using a preset questionnaire. The questionnaire recorded their basic disease and comorbidity, social and demographic characteristics, awareness of the various modalities of renal replacement therapy (RRT), and the reasons for choosing their present modality of therapy. Treating nephrologists were also interviewed with respect to the factors that, in their opinion, were responsible for the limited use of PD at our institute. RESULTS: In total, 342 patients on HD, 66 patients on PD, and 24 nephrologists were interviewed. The rate of PD use was 16.2%. Mean age of patients on HD and PD was 34.6 +/- 11.8 years and 62.9 +/- 10.3 years respectively (p < 0.0001). The incidence of diabetes mellitus and coronary artery disease in the HD and PD populations was 2.5% and 62.5%, and 9.1% and 46.7% respectively (p < 0.0001 for both). Only 30.4% of patients on HD were aware of PD as a modality of RRT and 83.6% of them found PD to be expensive, 65.4% had low enthusiasm toward a domiciliary therapy such as PD, and 61.5% were not recommended PD by their nephrologist. Only 5 (7.6%) patients were initiated on PD directly, the remaining 61 patients were shifted from HD after a mean duration on HD of 185.3 +/- 15.4 days: 67.1% were shifted due to poor tolerance of HD, 29.4% were advised to shift to PD because of comorbidity and vascular access problems, and only 3.3% took up PD because of the independent lifestyle it offered. None of the interviewed nephrologists routinely discussed PD in predialysis counseling. They found financial constraints (100%), lack of patient enthusiasm (100%), doubtful patient compliance (83.2%), and lack of an organized PD program (79.2%) to be the main factors limiting more widespread use of PD at our institute. CONCLUSIONS: Peritoneal dialysis is an underused modality of RRT at our institute. The patients who are taken up for PD at our institute are elderly and have a higher incidence of other comorbid conditions, such as diabetes mellitus and coronary artery disease. Also, most patients who switch to PD do so due to their unsuitability for HD rather than by their own choice. The factors contributing to this low rate of use of PD are ignorance of PD, increased cost of therapy, low enthusiasm toward domiciliary therapy, and lack of adequate infrastructure for PD at our institute. Effective predialysis counseling, reduction in the cost of the therapy, and development of an adequate infrastructure can increase the rate of use of PD.

Tranexamic acid overdosage-induced generalized seizure in renal failure.

We report a 45-year-old lady with chronic kidney disease stage 4 due to chronic tubulointerstial disease. She was admitted to our center for severe anemia due to menorrhagia and deterioration of renal function. She was infused three units of packed cells during a session of hemodialysis. Tranexamic acid (TNA) 1 g 8-hourly was administered to her to control bleeding per vaginum. Two hours after the sixth dose of TNA, she had an episode of generalized tonic clonic convulsions. TNA was discontinued. Investigations of the patient revealed no biochemical or structural central nervous system abnormalities that could have provoked the convulsions. She did not require any further dialytic support. She had no further episodes of convulsion till dis-charge and during the two months of follow-up. Thus, the precipitating cause of convulsions was believed to be an overdose of TNA.

Candida lung abscesses in a renal transplant recipient.

We herein report a renal allograft recipient five years post transplant who had bilateral lung abscesses. The abscess grew Candida tropicalis on bronchoalveolar lavage. The patient was administered amphotericin B, but succumbed to massive hemoptysis. The case highlights a fungal complication in renal transplant and need for early suspicion and prompt therapy.

Clinical relevance of curcumin-induced immunosuppression in living-related donor renal transplant: an in vitro analysis.

OBJECTIVES: In this study, we assessed the immunosuppressive potential of curcumin, a pharmacologically safe and cost-effective naturally occurring polyphenolic phytochemical, on the induction of Th1 cytokines that are frequently overexpressed in patients experiencing rejection after renal transplant. MATERIALS AND METHODS: Peripheral blood lymphocytes obtained from 68 renal transplant recipients and 17 healthy controls were treated with curcumin before stimulation with phorbol myristate acetate and were analyzed with flow cytometry for interferon-alpha and interleukin 4 positive cells. RESULTS: Patients experiencing acute rejection exhibited a high level of interferon-alpha (38.3% +/- 11.2%) and a low level of interleukin 4 (4.2% +/- 2.0%) in their activated peripheral blood lymphocytes. The use of curcumin dose-dependently decreased interferon-alpha induction in cultures from healthy controls (28.1% +/- 4.8%-10.7% +/- 5.3%, P < .001), patients experiencing acute rejection (38.3%-18.3%, P < .001), and those experiencing chronic rejection (40.6%-12.9%, P = .01) when compared with corresponding untreated cultures. In contrast, curcumin exerted only a marginal effect on interleukin 4 expression. Interestingly, curcumin was found to inhibit nuclear factor kappa beta activation by blocking the degradation of the inhibitory unit I kappa B alpha. We also noted the synergistic inhibitory effect of in vitro treatment with curcumin in combination with cyclosporine on the peripheral blood lymphocytes of patients experiencing acute rejection. CONCLUSIONS: These data provide a rationale for the use of curcumin as an affordable, pharmacologically safe, adjuvant immunosuppressant when used with cyclosporine and suggest that curcumin can effectively suppress Th1 cytokine induction after renal transplant.