The efficacy of isoniazid prophylaxis in renal transplant recipients in a high tuberculosis burden country.

INTRODUCTION: Renal transplant recipients are at high risk of tuberculosis (TB). We started isoniazid (INH) prophylaxis of 1 year duration in all renal transplant recipients from April 2009. Our aim was to assess the incidence of TB on INH prophylaxis and its tolerability. METHODS: This was a retrospective observational study. The files of renal transplant recipients from April 2009 to December 2011 were reviewed till June 2015. We noted the incidence of TB, INH tolerability, and development of resistance. We compared the incidence of TB with the historical controls who never received the prophylaxis. RESULTS: A total of 910 patients were reviewed and followed up for 4.8 years. INH prophylaxis was completed by 825 (91%) patients. A total of 46 patients (5%) developed active TB as compared to 15% in the historical controls. The median time of TB diagnosis from transplantation was 2.8 years. In the first-year post transplant, out of total TB cases, 52% occurred in the historical controls whereas 13% occurred in study cohort. Around 67% had TB >2 years after transplant. Overall 1.43% had hepatotoxicity. There was a significant reduction in TB among those who completed prophylaxis to those who did not (p < 0.001). Of 14 cultures, one isolate was INH resistant (7%). CONCLUSION: INH prophylaxis was well tolerated. The incidence of TB decreased in the first 2 years. However there was a surge in TB cases 1 year after stopping INH therapy. We should consider prolonging the duration of INH prophylaxis in high TB burden countries in renal transplant recipients.

Protection of Human Beings Trafficked for the Purpose of Organ Removal: Recommendations.

This report presents a comprehensive set of recommendations for protection of human beings who are trafficked for the purpose of organ removal or are targeted for such trafficking. Developed by an interdisciplinary group of international experts under the auspices of the project Trafficking in Human Beings for the Purpose of Organ Removal (also known as the HOTT project), these recommendations are grounded in the view that an individual who parts with an organ for money within an illegal scheme is ipso facto a victim and that the crime of trafficking in human beings for the purpose of organ removal (THBOR) intersects with the crime of trafficking in organs. Consequently, the protection of victims should be a priority for all actors involved in antitrafficking activities: those combating organ-related crimes, such as health organizations and survivor support services, and those combating trafficking in human beings, such as the criminal justice sectors. Taking into account the special characteristics of THBOR, the authors identify 5 key stakeholders in the protection of human beings trafficked for organ removal or targeted for such trafficking: states, law enforcement agencies and judiciary, nongovernmental organizations working in the areas of human rights and antitrafficking, transplant centers and health professionals involved in transplant medicine, and oversight bodies. For each stakeholder, the authors identify key areas of concern and concrete measures to identify and protect the victims of THBOR. The aim of the recommendations is to contribute to the development of a nonlegislative response to THBOR, to promote the exchange of knowledge and best practices in the area of victim protection, and to facilitate the development of a policy-driven action plan for the protection of THBOR victims in the European Union and worldwide.

Acute tubulointerstitial nephritis/drug induced acute kidney injury; an experience from a single center in Pakistan.

INTRODUCTION: There is no information in literature specifically on the prevalence and clinicopathological characteristics of acute tubulointerstitial nephritis/drug induced acute kidney injury (AKI) from Pakistan. OBJECTIVES: We aim to report a series of cases from patients developing AKI after exposure to some medications or finding of interstitial nephritis on histopathology. PATIENTS AND METHODS: This is an observational study of patients identified as having AKI after exposure to medications. AKI was defined according to RIFLE criteria and all patients fell from risk to loss category on arrival. On ultrasonography, all patients had normal size non-obstructed kidneys. Renal biopsy findings were consistent with tubule interstitial nephritis. RESULTS: Mean age of patients was 36.41 ± 17.40 years. Among total of 155, 80 were male and 75 female. Regarding drugs, most common was exposure to aminoglycoside in 34 (22%) followed by use of non-steroidal anti-inflammatory analgesics in 28, contrast induced agents in 11. Renal biopsy was performed in 58 patients. In half of these, insulting agent was not known and in rest either multiple medications were ingested or there was denial to substance use or recovery was delayed despite discontinuation of responsible medication. Renal replacement therapy was required on arrival in 119/155 (hemodialysis = 115, peritoneal dialysis = 4) cases. Complete renal recovery was observed in 71%, while 7.7% expired during acute phase, partial renal recovery was seen in 15% and 5% disappeared after first discharge from the hospital. CONCLUSION: Tubulointerstitial nephritis may occur with many drugs of common use. Early and intensive efforts must be made to consider and then timely correct the injury to the kidney.

Spectrum of glomerular diseases causing acute kidney injury; 25 years experience from a single center.

INTRODUCTION: Acute kidney injury (AKI) is common in nephro-urological practice. Its incidence, prevalence and etiology vary widely, mainly due to variations in the definitions of AKI. OBJECTIVES: We aim to report the spectrum of glomerular diseases presenting as AKI at a kidney referral center in Pakistan. PATIENTS AND METHODS: An observational cohort of patients identified as having AKI which was defined according to RIFLE criteria, with normal size, non-obstructed kidneys on ultrasonography, along with active urine sediment, edema and new onset hypertension. RESULTS: From 1990 to 2014, 236 cases of AKI secondary to acute glomerulonephritis (AGN) registered at this institution. Mean age of patients was 27.94± 12.79 years and M:F ratio was 0.77:1. Thirty percent patients revealed crescents on renal biopsy. AGN without crescents was seen in 33.05% of cases. Postinfectious GN was found in 14.4%, lupus nephritis in 8.5% and mesangiocapillary GN in 3.4% cases. Renal replacement therapy (RRT) required in 75.84% patients. Pulse steroids were given in 45.33% cases followed by oral steroids. Pulse cyclophoshphamide was given in 23.7% cases and plasmapheresis was used in 3.38% cases. Complete recovery was seen in 44%, while 11.44% died during acute phase of illness. About 19.49 % developed chronic kidney disease (CKD) and 25.84% were lost to long- term follow-up. CONCLUSION: Although glomerular diseases contribute only 4.19 % of total AKI at this center, morbidity associated with illness and its treatment is more marked than other AKI groups. Another notable factor is late referral of these patients to specialized centers resulting in undesirable outcome.

Azotemia protects the brain from osmotic demyelination on rapid correction of hyponatremia.

Osmotic demyelination syndrome (ODS) is a dreadful, irreversible and well-recognized clinical entity that classically occurs after rapid correction of hyponatremia. However, it has been observed that when hyponatremia is rapidly corrected in azotemic patients by hemodialysis (HD), patients do not necessarily develop ODS. We studied the effect of inadvertent rapid correction of hyponatremia with HD in patients with azotemia. Fifty-two azotemic patients, who underwent HD at the Sindh Institute of Urology and Transplantation, having pre-HD serum sodium level <125 mEq/L and post-HD serum sodium levels that increased by ≥12 mEq/L from their pre-dialysis level, were studied. Serum sodium was analyzed before and within 24 h after a HD session. HD was performed using bicarbonate solution, with the sodium concentration being 140 meq/L. The duration of the dialysis session was based on the discretion of the treating nephrologist. Patients were examined for any neurological symptoms or signs before and after HD and for up to two weeks. Magnetic resonance imaging was performed in required cases. None of the 52 patients with azotemia, despite inadvertent rapid correction of hyponatremia with HD, developed ODS. This study suggests that patients with azotemia do not develop ODS on rapid correction of hyponatremia by HD, which suggests a possible protective role of azotemia on the brain from osmotic demyelination. However, the mechanism by which azotemia protects the brain from demyelination in humans is largely hypothetical and further studies are needed to answer this question.

Range for normal body temperature in hemodialysis patients and its comparison with that of healthy individuals.

BACKGROUND/AIMS: Patients with chronic kidney disease undergoing hemodialysis have an altered homeostasis leading to altered body temperatures. We aimed to determine the range for normal body temperature in hemodialysis patients and compared it to healthy individuals. Also, we determined how much axillary temperatures differed from oral temperatures in both groups and whether axillary temperature is affected by the presence of an arteriovenous fistula (AVF) in hemodialysis patients. METHODS: Oral and axillary (left & right) temperatures were recorded using an ordinary mercury-in-glass thermometer in 400 subjects (200 hemodialysis patients, 200 healthy individuals) at the Sindh Institute of Urology and Transplantation from mid-May to mid-June 2006. Comparisons were made between the temperatures of both groups. RESULTS: Mean oral temperature in hemodialysis patients was higher than in healthy individuals [98.7 degrees F (37 degrees C) vs. 98.4 degrees F (36.8 degrees C); p < 0.001], as was the mean average axillary temperature [97.7 degrees F (36.5 degrees C) vs. 97.5 degrees F (36.3 degrees C); p = 0.02] and mean left axillary temperature [97.9 degrees F (36.6 degrees C) vs. 97.6 degrees F (36.4 degrees C); p < 0.001]. The fistula arm had higher axillary temperature in 77 (44%) hemodialysis patients. The difference between oral and axillary temperatures varied widely, making it impossible to obtain an accurate correction factor in both groups. CONCLUSION: Hemodialysis patients have higher normal body temperatures than healthy individuals. Axillary temperatures require cautious interpretation. In hemodialysis patients, the non-fistula arm should be preferred for recording axillary temperatures, as the presence of AVF may cause discrepancies in temperature measurements.

Use of isoniazid chemoprophylaxis in renal transplant recipients.

BACKGROUND: The use of isoniazid (INH) as chemoprophylaxis for tuberculosis (TB) in renal transplant recipients has not been widely studied or reported from a country where TB is endemic. We are reporting here the results of the largest ever-reported randomized, prospective study of the use of INH in renal transplant recipients. METHODS: Four hundred consecutive live related renal transplant recipients between April 2001 and September 2004, from this single center, were randomized to receive or not receive INH for 1 year after transplantation. RESULTS: There were 12 dropouts. Of the remaining 388, 181 recipients received INH for 1 year post-transplant and 207 did not. The primary disease, comorbidities, HLA (human leucocyte antigen) match, immunosuppression, episodes of rejection, the use of anti-rejection agents, a past history of TB in the donor, the recipients and in family members living in same house and a history of TB in the family were factors compared in the two groups. The only significant difference between the two groups was that there was an increased family history of TB in recipients who received INH (P = 0.01). One recipient from the INH group and 16 recipients from the non-INH group developed TB (P = 0.0003). Discontinuation of INH for hepatotoxicity was not required in any patient. CONCLUSION: These results provide evidence that the use of INH following renal transplantation should be considered mandatory in geographical areas where the prevalence of TB is high. Furthermore, these results have important implication in patients from such areas who are immunosuppressed following other kinds of transplantation and for those who are immunocompromised for any other reason.

Regulated compensated donation in Pakistan and Iran.

PURPOSE OF REVIEW: Paid living unrelated kidney donor transplantation has flourished in Pakistan and Iran. This review discusses the dynamics and consequences of organ trade in Pakistan and of a regulated paid donor model in Iran on transplant activities in these countries. RECENT FINDINGS: In 2007, over 2500 renal transplants were performed in Pakistan, where more than 70% were from socioeconomic disadvantaged kidney vendors. More than half of recipients were foreigners who paid US$20,000-30,000. Recipients of vendor kidneys had poor outcome and high infectious complications. Regulated paid donor kidney transplant in Iran number around 1500 per year and constitute 70% of the total transplants. Graft survival rates are similar to those for living related donors. The donors are paid US$1200 and additional monies are negotiated between the recipient-donor pair. This model claims to have abolished waiting lists, although many poor patients wait for deceased donors. In both countries, recipients are relatively rich and vendors are the poor of the society who sell kidneys for quick money or to repay debts. SUMMARY: Paid donation, regulated or commercial, leads to coercion and exploitation of the poor and benefits the rich. This situation has forestalled deceased donor program and hence other solid-organ transplants. The way forward is to promote deceased donors by making transplant available to all who need it.

Prognostic factors of survival in patients with non-resectable hepatocellular carcinoma: hepatitis C versus miscellaneous etiology.

OBJECTIVE: To identify prognostic determinants of survival in patients with non-resectable hepatocellular carcinoma (HCC), determine the effect of transarterial chemoembolization (TACE) on prognosis, compare hepatitis C related HCC with mixed etiologies and evaluate the prognostic value of different staging systems. METHODS: This cohort study included 129 patients (male = 97, 75%) with non-resectable HCC. Data was collected from 2002 until August 2006. A series of demographic, clinical and biochemical and radiological data were collected. Cases were staged according to the Child's, Okuda, Cancer Liver Italian program (CLIP), Barcelona Clinic Liver Cancer (BCLC) and Chinese University Prognostic Index (CUPI) systems. Survival analysis was performed. Any effect of TACE on prognosis was recorded. RESULTS: Median age of patients was 52 years (range 18-82). Median follow-up 11 months (range 2-36). At the time of analysis, 102 patients had died (79%). Etiology of HCC was hepatitis C virus (HCV) in 66 (51.2%), hepatitis B virus (HBV) 31 (24%), HBV + HCV 10 (7.8%), HBV + delta hepatitis 02 (1.6), and non-B non-C 20 (15.4%). Forty-one patients (31%) were offered TACE. Univariate analysis for HCV related HCC showed that age > 52 years (p<0.05), bilirubin >1.17 mg/dl (p<0.01), INR > 1.3 (p<0.01), alpha fetoprotein > 400 ng/ml (p<0.05), splenomegaly (p<0.01), ascites (p<0.001), portal vein thrombosis (p<0.01), splenic varices (p<0.01), and TACE not offered (p<0.01) were the prognostic factors while in miscellaneous etiology female sex (p<0.05), haemoglobin < 11.0 gm/dl (p<0.01), alkaline Phosphatase > 169 lU/L (p<0.05), ascites (p<0.05) and multifocality (p<0.05) were adversely effecting prognosis. Overall independent determinants were Hepatitis C etiology, female sex and multifocality of tumour (Hazard ratios 3.0, 3.0 and 1.9 respectively). Mean survival was 17.2 vs. 12.8 months for patients offered vs. not offered TACE respectively (p value = 0.015). Okuda, CLIP, BCLC, CUPI and Child's staging systems retained their performance as judged by chi square values in regression analysis. Discriminatory ability for death evaluated by receiver operating characteristic curve was better for Okuda system in the first year. CONCLUSION: Hepatitis C as the etiology of HCC, female sex and multi-focality are associated with poor prognosis. HCV related HCC may differ in prognostic factors from non-HCV HCC. Simple staging system by Okuda predicts prognosis effectively in non-resectable.

Range for normal body temperature in the general population of Pakistan.

OBJECTIVES: To determine the range for normal body temperature in the general population of Pakistan and to determine if any age, sex and ambient temperature related variations exist in body temperature. Moreover, to compare how much axillary temperature differs from oral temperature measurements. METHODS: Oral as well as left and right axillary temperature recordings were made using an ordinary mercury-in-glass thermometer in 200 healthy individuals accompanying patients at various clinics at the Sindh Institute of Urology and Transplantation (SIUT) between mid-May to mid-June 2006. Data analysis was done using Epi Info version 3.3. RESULTS: The range for Normal Oral Temperatures fell between 97 degrees F to 99.8 degrees F (mean 98.4 degrees F). There were no significant age related (p=0.68) and ambient temperature related variations (p=0.51) in body temperature, but women had slightly higher normal temperatures than men (mean 98.5 degrees F vs. 98.3 degrees F; p=0.01). A wide variation existed in the difference between oral and axillary temperatures, with axillary temperatures ranging up to 2.6 degrees F lower or up to 1.1 degrees F higher than the oral temperatures (mean difference = 0.85 degrees F). The correlation between oral and axillary temperatures increased at higher oral temperatures (p=0.009). CONCLUSION: There is a range for Normal Body Temperature and any temperature above 98.6 degrees F/37 degrees C is not necessarily pathological. Women appear to have higher body temperatures. As there is no uniform oral equivalent of axillary temperature, the latter should be interpreted with caution.

Bisphosphonate delivery to tubular bone allografts.

Large structural allografts used for reconstruction of bone defects after revision arthroplasty and tumor resection fracture up to 27% of the time from osteolytic resorption around the fixation screw holes and tendon or ligament attachment sites. Treating structural allografts before implantation with bisphosphonates may inhibit local osteoclastic processes and prevent bone resorption and the development of stress risers, thereby reducing the long-term fracture rate. Taking advantage of allografts' open-pore structure, we asked whether passive soaking or positive-pressure pumping was a more efficient technique for delivering bisphosphonates. We treated matched pairs of ovine tibial allografts with fluids containing Tc-99m pamidronate and toluidine blue stain to facilitate indicator distribution analysis via microSPECT-microCT imaging and light microscopy, respectively. Surfactants octylphenoxy polyethoxy ethanol or beractant were added to the treatment fluids to reduce flow resistance of solutions pumped through the allografts. Indicator distribution after 1 hour of soaking produced a thin ring around periosteal and endosteal surfaces, while pumping for 10 minutes produced a more even distribution throughout the allograft. Flow resistance was reduced with octylphenoxy polyethoxy ethanol but unaffected with beractant. Pumped allografts displayed a more homogeneous indicator distribution in less time than soaking while surfactants enhanced fluid movement.

Cryoglobulinaemia and autoimmune markers in hepatitis C virus infected patients on renal replacement therapy.

OBJECTIVE: To investigate the association of cryoglobulinaemia and autoimmune markers with hepatitis C virus (HCV) infection in patients on maintenance haemodialysis (HD) and post renal transplantation. METHODS: Serum samples of 103 HCV-antibody (anti-HCV) positive and 105 anti-HCV negative patients were investigated for cryoglobulins. These comprised 136 patients on HD and 72 renal transplant recipients. Serum creatinine and liver function tests were obtained on all patients. Rheumatoid factor (RF), anti nuclear antibodies (ANA), anti smooth muscle antibodies (ASMA), liver kidney microsomal antibodies (LKM), immunoglobulins (Igs) and complement levels were performed on all cryoglobulin positive (cryopositive) samples. HCV RNA and genotyping detection tests were done for cryopositive patients. RESULTS: The prevalence of cryoglobulins in patients on HD or after renal transplantation was found to be higher (57.6%) among anti-HCV positive patients compared to the anti-HCV negative patients (42.4%) (P=0.000). RF, ANA and ASMA were also higher in cryopositive HCV infected patients. HCV RNA was present in 84.2% of anti-HCV positive patients. Cryoprecipitable RF activity was found in a higher number of symptomatic patients with HCV genotype 1 compared to HCV genotype 3. CONCLUSION: There is an association of cryoglobulinaemia and autoimmune markers in HCV infected patients on HD, and in HCV positive renal transplant recipients. Also HCV genotype 1 is associated with symptomatic mixed cryoglobulinaemia.

Outcome in severe acute renal failure associated with malaria.

BACKGROUND: Malaria, a common health problem in certain parts of the world, has a considerable morbidity and mortality. This study reports its occurrence with a serious complication, acute renal failure (ARF), at a Third World tertiary care centre. METHODS: All registered patients with ARF who had history and clinical findings suggestive of malaria and had malarial parasites on peripheral blood smears were included in this study. The data on their modes of presentation, management and outcome have been analysed. RESULTS: Between January 1990 and December 1999, a total of 2098 patients with ARF were seen at the centre. Of these, 124 (5.9%) developed ARF due to malaria (falciparum in 121 and vivax in three). The male:female ratio was 4:1 and 84 (68%) patients were oligo- or anuric on presentation. Mean serum creatinine on admission was 9.43 +/- 5.39 mg/dl and 99 (79.8%) patients required renal replacement therapy. Of the cohort, 32 (25.8%) died, most within 48 h of admission. Age, oliguria, central nervous system involvement and presence of disseminated intravascular coagulopathy emerged as bad prognostic factors in simple univariate analysis. Of the survivors, 77 (62%) had complete recovery of renal function, while 15 (12%) were progressing towards recovery when lost to follow-up. The number of dialysis sessions did not differ significantly between the oliguric and non-oliguric groups. CONCLUSIONS: In patients who do not succumb early to ARF of severe malaria, treatment with antimalarials and dialysis brings about recovery of renal function.